Review ArticleQuorum Sensing A Prospective Therapeutic Targetfor Bacterial Diseases

Qian Jiang 123 Jiashun Chen1 Chengbo Yang3 Yulong Yin 1 and Kang Yao 1

1Laboratory of Animal Nutritional Physiology and Metabolic Process Institute of Subtropical AgricultureChinese Academy of Sciences China2University of Chinese Academy of Sciences Beijing 100043 China3Department of Animal Science University of Manitoba Winnipeg MB Canada R3T 2N2

Correspondence should be addressed to Kang Yao yaokangisaaccn

Received 29 January 2019 Accepted 20 March 2019 Published 4 April 2019

Guest Editor Deguang Song

Copyright copy 2019 Qian Jiang et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Bacterial quorum sensing (QS) is a cell-to-cell communication in which specific signals are activated to coordinate pathogenicbehaviors and help bacteria acclimatize to the disadvantages The QS signals in the bacteria mainly consist of acyl-homoserinelactone autoinducing peptide and autoinducer-2QS signaling activation and biofilm formation lead to the antimicrobial resistanceof the pathogens thus increasing the therapy difficulty of bacterial diseases Anti-QS agents can abolish theQS signaling andpreventthe biofilm formation therefore reducing bacterial virulence without causing drug-resistant to the pathogens suggesting that anti-QS agents are potential alternatives for antibiotics This review focuses on the anti-QS agents and their mediated signals in thepathogens and conveys the potential of QS targeted therapy for bacterial diseases

1 Introduction

Antibiotics have been commonly used to prevent bacterialinfection and diseases for many decades since their discoveryat the beginning of the 20th century However emergingevidence [1ndash6] indicates that traditional antibiotic treatmentstend to be ineffective for the patients due to the emergence ofdrug-resistant pathogens resulting from antibiotics overuse[7 8] The fact that bacterial infection annually deprivesabout 16 million human lives prompts us to develop novelapproaches fighting against the drug-resistant pathogens andrelated diseases [9]

Bacterial quorum sensing (QS) signaling can be acti-vated by the self-produced extracellular chemical signalsin the milieu The QS signals mainly consist of acyl-homoserine lactones (AHLs) autoinducing peptides (AIPs)and autoinducer-2 (AI-2) all of which play key roles in theregulation of bacterial pathogenesis For instance studies[10ndash12] reported that QS signals participate in the synthesisof virulence factors such as lectin exotoxin A pyocyaninand elastase in the Pseudomonas aeruginosa during bacte-rial growth and infection The synthesis and secretion of

hemolysins protein A enterotoxins lipases and fibronectinprotein are regulated by the QS signals in the Staphylococcusaureus [13 14] These virulence factors regulated by QS helpbacteria evade the host immune and obtain nutrition fromthe hosts

The anti-QS agents which are considered as alternativesto antibiotics due to its capacity in reducing bacterial vir-ulence and promoting clearance of pathogens in differentanimal model have been verified to prevent the bacterialinfection The clinical application of anti-QS agents is stillnot mature This review builds on the increasing discoveriesand applications of the anti-QS agents from the studies inthe past two decades Our goal is to illustrate the potentialof exploiting the QS signals-based drugs and methods forpreventing the bacterial infection without resulting in anydrug-resistance of pathogens

2 Quorum Sensing Signals

The bacterial QS signals mainly consist of acyl-homoserinelactones (AHLs) autoinducing peptides (AIPs) and

HindawiBioMed Research InternationalVolume 2019 Article ID 2015978 15 pageshttpsdoiorg10115520192015978

2 BioMed Research International

autoinducer-2 (AI-2) and participate in the various physio-logical processes of bacteria including biofilm formationplasmid conjugation motility and antibiotic resistance bywhich bacteria can adapt to and survive from disadvantages[15] The Gram-negative and Gram-positive bacteria havedifferent QS signals for cell-to-cell communications TheAHL signaling molecules are mainly produced by Gram-negative bacteria [16] and AIP signaling molecules areproduced by the Gram-positive bacteria [17] Both Gram-negative and Gram-positive bacteria produce and sensethe AI-2 signals [18] These three families of QS signals aregaining more and more attention due to their regulatoryroles in bacterial growth and infection

Lux-I type AHL synthase circuit has been consideredas the QS signals producer in the Gram-negative bacte-ria [19] Once the AHLs accumulate in the extracellularenvironment and exceed the threshold level these signalmolecules will diffuse across the cell membrane [20] andthen bind to specific QS transcriptional regulators therebypromoting target gene expression [21] The signal moleculesAIPs are synthesized in Gram-positive bacteria and secretedby membrane transporters [17] When an environmentalconcentration of AIPs exceeds the threshold these AIPs bindto a bicomponent histidine kinase sensor whose phospho-rylation in turn alters target gene expression and triggersrelated physiological process [22] For instance QS signals inStaphylococcus aureus are strictly regulated by the accessorygene regulator (ARG) which associated with AIPs secretion[23 24] ARG genes are involved in the production of manytoxins and degradable exoenzymes [25] which are mainlycontrolled by P2 and P3 promoters [26 27] The AGR genesalso participate in the encoding of AIPs and the signalingtransduction of histidine kinase [28] Bacteria can sense andtranslate the signals from other strains in the environmentknown as AI-2 interspecific signals AI-2 signaling in mostbacterial strains is catalyzed by LuxS synthase [29 30] LuxSis involved not only in the regulation of the AI-2 signals butalso in the activated methyl cycle and has been revealed tocontrol the expressions of 400more genes associated with thebacterial processes of surface adhesion movement and toxinproduction [31]

3 Biofilm Formation and Virulence Factors

Bacteria widely exist in the natural environment on thesurface of hospital devices and in the pathological tissues[32] Biofilm formation is one of the necessary requirementsfor bacterial adhesion and growth [33] The biofilm for-mation is accompanied by the production of extracellularpolymer and adhesion matrix [34 35] and leads to funda-mental changes in the bacterial growth and gene expression[36] The formation of biofilm significantly reduces thesensitivity of bacteria to antibacterial agents [37 38] andradiations [39] and seriously affects public health Someformidable infections are associated with the formation ofbacterial biofilms on the pathological tissues andmost infec-tions induced by hospital-acquired bloodstream and urinarytract are caused by biofilms-coated pathogens on hospital

medical devices A large number of studies [33 40 41] haveshown that bacterial quorum sensing (QS) signaling playsimportant roles in biofilm formation Specific QS signalingblockage is considered an effective means to prevent thebiofilms formation of most pathogens thereby increasing thesensitivity of pathogens to antibacterial agents and improvingthe bactericidal effect of antibiotics [42 43]

The production of virulence factors which could helpbacteria evade the hosts immune response and cause patho-logical damage is crucial for the pathogenesis of infections[44ndash46] The virulence factors produced by different strainsare different For example Gram-negative Pseudomonasaeruginosa produces virulence factors such as pyocyaninelastase lectin and exotoxin A [47 48] and Gram-positiveStaphylococcus aureus produces virulence factors such asfibronectin binding protein hemolysin protein A lipase andenterotoxin [49 50] Studies have shown that the productionof these virulence factors is regulated by the bacterial QSsignaling systems [51 52] Disruption of QS to control theproduction of virulence factors seems to be an attractivebroad-spectrum therapeutic strategy

4 Strategies for QS Disruption

The fact pathogens colonized in the host must active theQS signaling to form biofilm and produce virulence factorssuggests that breaking this bacterial rdquoconversationrdquo by anti-QS agents makes pathogens more susceptible to host immuneresponses and antibiotics In this section we discuss the QSdisruption strategies including receptor inactivation signalssynthesis inhibition signals degradation signaling blockageby antibody and combining use with antibiotics and conveythe potential of QS as the therapeutic target for bacterialdiseases

41 QS Receptor Inactivation Inactivation of receptors inQS signaling is an effective strategy for reducing bacte-rial virulence and infection (Table 1) Studies [53] havedemonstrated that flavonoids can bind to QS receptorsand significantly reduce the virulence gene expression inPseudomonas aeruginosa N-decanoyl-L-homoserine benzylester a structural analog of AHL signals has been revealedto reduce the production of virulence factors such as elastaseand rhamnolipid by blocking the homologous receptors inPseudomonas aeruginosa [54 55] Receptor antagonists havebeen revealed to enhance the antibacterial activity of variousantibiotics and minimize the therapeutic dose of antibi-otics for Pseudomonas aeruginosa infection [56] The meta-bromo-thiolactone was reported to prevent Pseudomonasaeruginosa infection by decreasing the pyocyanin productionand inhibiting the biofilm formation [57] Geske et al havedeveloped AHLs analogs that can bind with the LuxRTraR and LasR receptors in Vibrio fischeri Agrobacteriumtumefaciens and Pseudomonas aeruginosa respectively [58]However the application of receptor inhibitors for treatingbacterial diseases is lagging behind due to the propertiesof instability and degradability within alkaline conditionsFurther studies are warranted to improve the stability of theseeffective anti-QS agents

BioMed Research International 3

Table1Stud

iesdemon

stratingthequ

orum

sensing(Q

S)sig

nalin

gdisrup

tionby

receptor

inactiv

ation

Abbreviatio

ns3

-oxo-C

12N

-3-oxodo

decano

yl-C

12A

HL

N-acyl-h

omoserine

lacton

esA

Iautoindu

cerC4

-LHL

butenylh

omoserinelactonesC6

-LHLhexano

ylho

moserinelactonesHSLL-hom

oserinelactonePHLprop

ionylh

omoserinelactones

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

In-vitro

Pseudomonas

aerugin

osa

Flavon

oids

Allo

steric

inhibitio

nof

AI-bind

ing

receptorsLasR

andRh

lR

Alteredtranscrip

tionof

QS-controlledtarget

prom

otersa

ndsupp

resses

virulencefactor

prod

uctio

n[53]

In-vitro

Pseudomonas

aerugin

osaPA

O1

N-decanoyl-L

-hom

oserine

benzylester

Activ

atingq

uorum

sensingcontrolrepressor

Attenu

ated

thea

ctivity

ofprotease

andelastase

swarmingmotility

andbiofi

lmform

ation

[5455]

In-vitro

Cele

gansA

549cells

Pseudomonas

aerugin

osaPA

14Meta-brom

o-thiolacton

eInhibitio

nof

LasR

andRh

lRInhibitedbo

ththep

rodu

ctionof

thev

irulencefactor

pyocyaninandbiofi

lmform

ation

[57]

In-vitro

Pseudomonas

aerugin

osa

AHLligands

A4

4-brom

ophenyl-P

HLB7

4-iodo

PHLC1

0and

3-nitro

PHLC14

Bind

ingto

TraR

LasR

and

LuxR

Strong

lyinhibitedvirulencefactorp

rodu

ction

[58]

In-vitro

Mice

Aeromonas

hydrophila

C4-a

ndC6

-HSLs

3-oxo-C1

2-HSL

Regu

latin

gtheh

ostimmun

ereceptor

Increasedsurvivability

ofinfected

mice

[59]

4 BioMed Research International

42 QS Signals Synthesis Inhibition The acyl-homoserinelactone molecules (AHLs) not only participate in bacterialcommunication but also play roles in conversations witheukaryotic cells AHLs can regulate the signaling pathwaysin epithelial cells and affect the behavior of innate immunecells [59 60] Inhibiting the synthesis of AHLs is a directstrategy to reduce AHL-mediated virulence factors andprevent pathological damage (Table 2) For example studieshave revealed that the sinefungin butyryl-SAM and S-adenosylhomocysteine can attenuate the secretion of QS-mediated virulence factors and prevent the bacterial infectionby inhibiting the AHLs synthesis in Pseudomonas aeruginosa[61ndash63] Singh et al reported that immucillin A and itsderivatives can reduce the AHLs synthesis by inhibiting the5-MTANS-adenosylhomocysteine nucleosidase [64] Thetriclosan has been verified to reduce AHL synthesis byinhibiting the production of enoyl-ACP reductase precursors[65 66] However these agents for AHLs synthesis inhibitionalso block the metabolism of amino acid and fatty acidthat play key roles in bacterial basic nutrition [67] Thefact that triclosan increased the antibiotic-resistance of Pseu-domonas aeruginosa implies selective pressure on bacteriawere triggered by the blocking effects of triclosan on themetabolism of amino acid and fatty acid in the bacteria[68] The triclosan is considered as bioindicator pollutiondue to its potential in causing the drug-resistance of thepathogens and increasing human health risks [69] Thusthe drugs specifically targeting AHLs synthesis inhibitionwithout blocking nutritional metabolisms of bacteria shouldbe developed and identified by sufficient in vitro experimentsbefore their clinical application

43 QS Signals Degradation Degradation of QS signals byenzymes can effectively disrupt the ldquocommunicationrdquo amongthe bacteria without causing any selective pressure to thebacteria The enzymes consist of lactonase acylase oxidore-ductases and 3-Hydroxy-2-methyl-4(1H)-quinolone 2 4-dioxygenase all of which are derived from different bacterialstrains and have been applied for QS signals degradation(Tables 3 and 4)

The AHL lactonase a member of Metallo-120573-lactamasesuperfamily was able to prevent bacterial infection by de-grading AHLs with different length of side chain [70 71]TheAHL lactonases were reported to increase bacterial sensitivityto antibiotics without affecting the growth of Pseudomonasaeruginosa [72 73] and Acinetobacter baumannii [74] TheAHL lactonase also has been applied to block the biofilmformation of Pseudomonas aeruginosa [75ndash77] The AHLlactonase AiiK produced by the engineered Escherichia coliwas revealed to inhibit extracellular proteolytic activity andpyocyanin production of Pseudomonas aeruginosa PAO1[78] In addition synergistic action of AHL lactonase andantibiotics was observed in the mice model infected withPseudomonas aeruginosa that is the drugs containing AHLlactonase can effectively inhibit the spread of skin pathogenswhile minimizing the effective dose of antibiotics The AHLlactonase has also been applied in the fishery industry forinstance Liu et al reported the lactonaseAIO6 supplementedto tilapia was able to prevent the Aeromonas hydrophila

infection [79] Studies reported the lactonase AiiA candecrease the virulence and inhibit biofilm formation ofVibrioparahaemolyticus in shrimps [80 81]

The acylase which was initially found in Variovoraxparadoxus and Ralstonia can block the QS signaling byhydrolyzing the amide bond of AHLs [82ndash84] The acylasewas revealed to decrease the growth of Pseudomonas aerug-inosa ATCC 10145 and PAO1 by 60 [85 86] and has beenwidely applied in humanhealth care for example the acylase-coated device showed a well antibacterial property due to theQS signaling disruption by the acylase [87] The acylase isalso chemically immobilized on some nanomaterials to act asan antifouling agent [88] Undoubtedly these applications ofacylase will greatly reduce the health care cost caused by thespread and colonization of pathogenic bacteria on medicaldevices

Oxidoreductases are enzymes that can affect the AHLsspecificity of homologous intracellular receptors by modi-fying acyl side chains thus interfering with the expressionof QS related virulence genes [89] Previous studies havedemonstrated the secretion of oxidoreductases by bacteriaas a protective mechanism instead of a pathogenic sig-naling [90] The BpiB09 oxidoreductase was reported toinhibit the activation of N-3-oxo-dodecanoyl homoserinelactone (3-oxo-C12-HSL) in the Pseudomonas aeruginosaPAO1 and decrease bacterial motility biofilms formation andpyocyanin secretion [91] Immobilization of oxidoreductaseson the glass surface can inhibit the bacterial biofilm forma-tion and decrease the growth rate of Klebsiella oxytoca andKlebsiella pneumoniae [92 93]

The dioxygenase has been revealed to block the quin-olone signals in the QS system of Pseudomonas aerugi-nosa [94] Dioxygenase can degrade 2-heptyl-3-hydroxy-4 (1H)-quinolone mediated signals and decreases signalingmolecules accumulation in the bacterial milieu thereforereducing the secretion of pyocyanin rhamnolipid and lectinA toxin which protects the host from infective damage [9596]

Together the anti-QS signaling enzymes are promisingalternatives to antibiotics that can be used not only to controlbacterial infection but also to minimize the risk of causingantibiotic-resistant strains However the stability of enzymesin vivo is the most difficult problem for their biomedicalapplications It is of great significance to study and developthe stability of the anti-QS signaling enzymes in vivo QSdegradation by nonpathogenic bacteria is an effective strategyfor QS disruption Pectobacterium carotovorum subsp caro-tovorum is a preferred and commonly used bacterial strainforQS degradation [97]This biological strategy for QS signaldegradation has been applied to prevent plant diseases [98]but has not been applied for human diseases treatment Byexploring novel QS-degradation strains it might be possibleto cure the chronic diseases caused by the antibiotic-resistantpathogens

44 Target Antibodies for QS Blockage Theactivation of AHLand AI-2 signaling can induce programmed cell death byaffecting the hosts immune system [59 99] Kaufmann et

BioMed Research International 5

Table2Stud

iesd

emon

stratingtheQ

Sdisrup

tionby

signalssynthesis

inhibitio

nAb

breviatio

nsA

Iautoindu

cerenoyl-A

CPeno

yl-acylcarrie

rproteinH

SLL

-hom

oserinelactoneP

HL

prop

ionylh

omoserinelactones

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

In-vitroRa

tsStreptococcus

pneumoniaeD

-39

Sinefung

inInhibitio

nof

AI-2synthesis

via

downregulatinglux

SpfsandspeE

expressio

nInhibitedpn

eumococcalbiofilm

grow

thin

vitro

and

middlee

arcolonizatio

nin

vivo

[62]

In-vitro

Pseudomonas

aerugin

osa

Sinefung

inbutyryl-SAM

and

S-adenosylho

mocysteine

Inhibitin

gacyl-H

SLsig

nals

Inhibitedform

ationof

acovalentacylndashenzyme

[61]

In-vitro

Escherich

iacoli

Methylth

io-D

ADMe-

immucillin-A

Dow

nregulating51015840-m

ethylth

ioadenosine

S-adenosyl-hom

ocysteinen

ucleosidase

hydrolyzes

Disr

uptedkeybacterialpathw

ayso

fmethylatio

npo

lyam

ines

ynthesis

methion

ines

alvageand

quorum

sensing

[64]

Mou

sePlasmodium

falciparum

Triclosan

Inhibitin

genoyl-A

CPredu

ctase

Protectedagainstb

lood

stageso

fmalariaenh

anced

elastic

strength

[66]

6 BioMed Research International

Table3Stud

iesd

emon

stratingQSdisrup

tionby

signalsdegradation

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

In-vitro

Pseudomonas

aerugin

osa

Lacton

aseS

soPo

xDegradatio

nof

thea

cyl-h

omoserinelactones

Inhibitedthev

irulenceo

f51clin

icalPaerugino

saiso

latedfro

mdiabeticfoot

ulcersby

decreasin

gthe

secretionof

proteasesa

ndpyocyanin

andbiofi

lmform

ation

[72]

In-vitrorats

Pseudomonas

aerugin

osaPA

O1

Lacton

aseS

soPo

x-1

Degradatio

nof

thea

cyl-h

omoserinelactones

Decreased

lasB

virulenceg

enea

ctivitypyocyanin

synthesisproteolyticactiv

ityand

biofi

lmform

ation

Redu

cedthem

ortalityof

ratswith

acutep

neum

onia

from

75to

20A

ttenu

ated

lung

damageo

fthe

rat

mod

el

[73]

In-vitro

AbaumanniiS1S

2S3

Engineered

lacton

ase

Degradatio

nof

thea

cyl-h

omoserinelactones

Redu

cedtheb

iomasso

fAbaumanniiassociated

biofi

lms

[74]

In-vitro

Pseudomonas

aerugin

osa

Lacton

aseA

ii810

Degradatio

nof

thea

cyl-h

omoserinelactones

Attenu

ated

VirulenceF

actorsandBiofi

lmFo

rmationDegradedN-butyryl-L-hom

oserine

lacton

eand

N-(3-oxod

odecanoyl)-L-ho

moserine

lacton

eby

723and100

[75]

In-vitro

Pseudomonas

aerugin

osa

Overexpressionof

lacton

asee

nzym

eAHL-1

Degradatio

nof

thea

cyl-h

omoserinelactones

Redu

cedthep

roteasepyocyanin

rham

nolip

ids

Inhibitedthea

ctivities

onthes

warmingmotility

and

biofi

lmform

ation

[76]

In-vitro

Pseudomonas

aerugin

osa

NovelLacton

asec

lonedby

bpiB01bpiB0

4Degradatio

nof

the

N-(3-oxoo

ctanoyl)-L-ho

moserinelactone

Inhibitedmotility

andbiofi

lmform

ation

[77]

In-vitro

Pseudomonas

aerugin

osaPA

O1

Lacton

aseA

iiKDegradatio

nof

thea

cyl-h

omoserinelactones

Inhibitedtheb

iofilm

form

ationandattenu

ates

extracellularp

roteolyticactiv

ityandpyocyanin

prod

uctio

n[78]

In-vitro

Pseudomonas

aerugin

osaPA

O1

N-Acyl-H

omoserine

Lacton

eAcylase

PA2385

Degradatio

nof

3-oxo-C1

2-HSL

and

2-heptyl-3-hydroxy-4(1H)-

quinolon

e

Redu

cedprod

uctio

nof

thev

irulencefactorselastase

andpyocyanin

[85]

In-vitroC

elegans

Pseudomonas

aerugin

osaPA

O1

NADP-depend

ent

short-c

hain

dehydrogenaseredu

ctase

(bpiB0

9)

Inactiv

ationof

N-(3-oxo-do

decano

yl)-L-ho

moserinelactone

(3-oxo-C

12-H

SL)

Redu

cedpyocyaninprod

uctio

ndecreasedmotility

poor

biofi

lmform

ationandabsent

paralysis

ofC

elegans

[91]

In-vitroplant

Pseudomonas

aerugin

osaPA

O1

3-hydroxy-2-methyl-4

(1H)-

quinolon

e

Catalyzingthec

onversionof

PQSto

N-octanoylanthranilica

cidandcarbon

mon

oxide

R edu

cedexpressio

nof

theP

QSbiosyntheticgene

pqsA

expressionof

theP

QS-regu

latedvirulence

determ

inantslectin

Apyocyaninand

rham

nolip

ids

andvirulenceinplant

[94]

BioMed Research International 7

Table4Ap

plications

involvingwith

AHLs

degradationby

anti-QSa

gents3-oxo-C1

2N-3-oxodo

decano

yl-H

SLA

HLN-acyl-h

omoserinelactonesC4

-LHLbu

tenylhom

oserinelactones

C6-LHL

hexano

ylho

moserinelactones

Objectiv

esStrains

Anti-Q

Sagents

Target

Effects

Ref

Tilapia

Aeromonas

hydrophila

AHLlacton

aseA

IO6

Degradatio

nof

thea

cyl-h

omoserinelactones

Maintainedthem

icrovilli

leng

thin

theforegut

oftilapiabut

significantly

lowe

rthanthoseo

fthe

control

[79]

Shrim

pandclam

Vibriona

ceae

strains

Deletionof

AHLs

genesin

34marineV

ibrio

naceae

strains

Acyl-hom

oserinelactonesinactivation

Redu

cedvirulencea

ndmortalityof

them

utant

strains

inbrines

hrim

pandManila

clam

[80]

Shrim

pVibrio

parahaem

olyticu

sAHL-lacton

ase

(AiiA

)Degradatio

nof

thea

cyl-h

omoserinelactones

Inhibitedvibrio

biofi

lmdevelopm

entand

attenu

ated

infectionandmortalityRe

duce

vibrio

viablecoun

tsandbiofi

lmdevelopm

entintheintestin

e[81]

Enzymem

ultilayer

coatings

Chromobacteriu

mviolaceum

CECT

5999Pseud

omonas

aerugin

osaAT

CC

10145

Acylasefrom

Aspergillus

melleus

Degradatio

nof

C6-LHL

Inhibited50violaceinprod

uctio

nby

Chromobacteriu

mviolaceum

CECT

5999R

educes

theP

seud

omonas

aerugin

osaAT

CC10145b

iofilm

form

ationun

derstatic

anddynamiccond

ition

s

[86]

Acylase-containing

polyurethane

coatings

Pseudomonas

aerugin

osaAT

CC

10145a

ndPA

O1

Acylasefrom

Aspergillus

melleus

Degradatio

nof

C4-LHL

C6-LHL

and

3-oxo-C1

2-LH

L

Immob

ilizatio

nof

acylaseled

toan

approxim

ately

60redu

ctionin

biofi

lmform

ation

redu

cethe

secretionof

pyocyanin

[87]

Immob

ilizatio

non

Nanofi

bers

Pseudomonas

aerugin

osaPA

O1

Acylase(EC

35114)

Degradatio

nof

AHLindu

cers

Redu

cedtheb

iofilmbiofoulingform

ationun

der

static

andcontinuo

usflo

wcond

ition

s[88]

8 BioMed Research International

Table5Stud

iesd

emon

stratingQSdisrup

tionby

antib

odiestargetin

g

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

In-vitroandRA

W2647cells

Pseudomonas

aerugin

osa

Antibod

yRS2-1G9

generatedagainsta

3-oxo-do

decano

ylho

moserinelactone

analog

hapten

Targetingtheb

acteria

lN-3-oxo-dod

ecanoyl

homoserinelactone

molecules

Protectm

urineb

onem

arrow-derived

macroph

ages

from

thec

ytotoxiceffectsandalso

preventedthe

activ

ationof

them

itogen-activ

ated

proteinkinase

p38

[100]

In-vitro

Pseudomonas

aerugin

osa

Antibod

yXYD

-11G

2Hydrolyzing

N-3-(oxod

odecanoyl)-L-ho

moserine

lacton

eSupp

ressed

QSsig

nalin

g[101]

In-vitroandmou

semod

elStaphylococcus

aureus

Antibod

yAP4

-24H

11elicitedagainsta

ratio

nally

desig

nedhapten

Sequ

estrationof

thea

utoind

ucingp

eptid

e-4

Supp

ressed

Saureus

pathogenicity

inan

abscess

form

ationmou

semod

elin

vivo

andprovided

completep

rotectionagainsta

lethalStaphylococcus

aureus

challenge

[103]

BioMed Research International 9

Table6Stud

iesd

emon

stratingthes

ynergistice

ffectso

fanti-Q

Sagentsandantib

iotic

s

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

Mice

Pseudomonas

aerugin

osa

Furano

neC-

30ajoeneo

rho

rseradish

juicee

xtractin

Com

binatio

ncurcum

in

QSinhibitio

nenhancethe

sensitivity

ofpathogen

toantib

iotic

sRe

sultedin

anincreasedclearanceo

fPseud

omonas

aerugin

osain

aforeign

-bod

yinfectionmod

el

[107]

In-vitro

Pseudomonas

aerugin

osa

with

tobram

ycin

gentam

icin

and

azith

romycin

Indu

cedconcentrations

ofC1

2-ho

moserine

lacton

eand

C4-h

omoserinelactone

Curcum

inshow

edsynergisticeffectswith

azith

romycin

andgentam

icinC

ombinatio

nuse

redu

cedQS-relatedvirulencefactors

Dow

nregulated

QS-relatedgenes

[112]

In-vitro

Staphylococci

Epigallocatechin-3-gallate

with

Tetracyclin

eInhibitio

nof

thea

ctivity

ofTet(K

)pum

pseffl

uxpu

mps

ofad

ifferentclassTet(B

)En

hanced

theb

acteric

idaleffecto

fTetracyclineo

nStaphylococci

[113]

In-vitro

Pseudomonas

aerugin

osa

N-(2-pyrim

idyl)

butanamideC1

1Dow

nregulationof

rhlrhlA

andlasB

genes

Increasedthes

usceptibilityto

antib

iotic

sand

attenu

ated

thep

atho

genicityof

theb

acteriu

m

[115]

In-vitro

Staphylococcus

aureus

(methicillin-resistant

Sau

reus)

Farnesolwith120573-la

ctam

antib

iotic

s

Inhibitio

nof

lipasea

ctivity

anddisrup

tionof

thec

ytop

lasm

icmem

branethrou

ghthe

leakageo

fpotassiu

mions

Attenu

ated

ther

ateo

fgrowth

ofbacteriaand

coun

terin

gub

iquitous120573-la

ctam

resistancein

bacteria

[116117]

In-vitro

Cele

gansG

aller

iamellonellamice

Burkholderia

cenocepacia

Staphylococcus

aureus

Escherich

iacoli

Baicalin

hydrate

cinn

amaldehyde

hamam

elitann

inwith

Tobram

ycinvancomycin

andclindamycin

Inhibitio

nof

biofi

lmform

ation

QSinhibitio

nenhancethe

sensitivity

ofpathogen

toantib

iotic

s

Com

bining

theu

seof

antib

odyandanti-QSagents

increasedsusceptib

ilityof

theb

acteria

tothe

antib

iotic

and

increasedho

stsurvivalrateaft

erinfection

[118]

10 BioMed Research International

al found in their study [100] that the antibody RS2-1G9can bind to 3-oxo-C12-HSL in the extracellular environmentof Pseudomonas aeruginosa thereby attenuating the inflam-matory response of the host XYD-11G2 antibody has beenshown to catalyze the hydrolysis of 3-oxo-C12-HSL signalingthus inhibiting the pyocyanin production by Gram-negativebacteria [101 102] The monoclonal antibody AP4-24H11 wasfound to block the QS signal of Gram-positive Staphylococcusaureus by interfering with AIP IV [103] Another in vivo studyshowed that the antibody AP4-24H11 could significantlyattenuate the tissue necrosis in the infected model [104]Although these monoclonal antibodies have been identifiedto block the QS signaling of pathogenic bacteria (Table 5)their applications for treating bacterial diseases are still in theinitial stage

45 Combinations of Anti-QS Agents and Antibiotics Com-bining use of antibiotic with an anti-QS agent is the mosteffective clinical strategy for the treatment of bacterial dis-eases at present [105 106] Many studies have confirmed thesynergistic effect of antibiotics and anti-QS agents (Table 6)Ajoene furanone c-30 and horseradish extract have beenrevealed to reduce the expression of virulence factors inPseudomonas aeruginosa and make Pseudomonas aeruginosaeasier to be cleared by tobramycin [107ndash111] Another studyhas confirmed the synergistic effects of curcumin gentam-icin and azithromycin on Pseudomonas aeruginosa that isthe expressions of virulence genes were significantly down-regulated by the combining use of curcumin together withgentamicin or azithromycin and the therapeutic doses ofgentamicin and azithromycin were minimized by curcuminsupplementation [112] The anti-QS compounds such asgallocatechin 3-gallate and caffeic acid enhanced therapeuticeffects on Mycoplasma pneumoniae infection by combininguse with tetracycline ciprofloxacin or gentamicin [113 114]N-(2-pyrimidyl) butylamine was confirmed to enhance theantibacterial effect of tobramycin colistin and ciprofloxacinon Pseudomonas aeruginosa [115] Recent studies [116 117]have shown that both farnesol and hamamelitannin canreduce the virulence of Staphylococcus aureus and increasethe sensitivity of Staphylococcus aureus to 120573-lactam antibi-otics Synergistic effects of hamamelitannin baicalin hydratecinnamaldehyde and antibiotics have been demonstrated indifferent infection models [118 119]These findings imply thatcombining use of antibiotics with ant-QS agents has greattherapeutic potential for bacterial diseases

5 Conclusions

Regulating bacterial QS signaling by QS-targeted agents isan effective strategy to control the production of bacte-rial virulence factors and the formation of biofilm Thisnovel nonantibiotic therapy can inhibit the expression ofpathogenic genes prevent infection and reduce the riskof drug resistance of bacterial cells and has been widelyexploited in recent years A large number of studies haveidentified many anti-QS agents to control the pathogenicphenotypes ofmost bacteria and to attenuate the pathological

damage in various animal infection models However mostanti-QS agents are still in the preclinical phase and morehuman clinical trials are warranted to test their practicalfeasibility The results of several existing clinical studies [120ndash122] on anti-QS agents show that compared with antibioticsthe anti-QS compounds may have potential toxicity andtheir therapeutic effect is not as stable as that of antibioticswhich limited their extensive application Combining use ofanti-QS agents with conventional antibiotics can significantlyimprove the efficacy of therapeutic drugs and decrease thecost of human healthcare and is likely to be the mainapplication method of anti-QS agents for bacterial diseasestreatment in the future

Conflicts of Interest

The authors declare that there are no conflicts of interestregarding the publication of this paper

Acknowledgments

The authors are thankful to the China Scholarship Council(CSC) for both financial support and scholarships Theauthors appreciate Dr Ruiqiang Yang at the Nanjing Agri-culture University for his help on this review This workwas supported by the National Natural Science Foundationof China (31472107) the Youth Science Fund Project of theNational Natural Science Foundation of China (31702126)the Chinese Academy of Sciences lsquoHundred Talentrsquo awardthe National Science Foundation for Distinguished YoungScholars of Hunan Province (2016JJ1015) the Postgradu-ate Research and Innovation Project of Hunan Province(CX2017B348) the Hunan Province ldquoHunan Young Scienceand Technology Innovation Talentrdquo Project (2015RS4053)the Hunan Agricultural University Provincial Outstand-ing Doctoral Dissertation Cultivating Fund (YB2017002)and the Open Foundation of Key Laboratory of Agro-ecological Processes in Subtropical Region Institute ofSubtropical Agriculture Chinese Academy of Sciences(ISA2016101)

References

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[2] F E Akram T El-Tayeb K Abou-Aisha and M El-AzizildquoA combination of silver nanoparticles and visible blue lightenhances the antibacterial efficacy of ineffective antibioticsagainst methicillin-resistant Staphylococcus aureus (MRSA)rdquoAnnals of Clinical Microbiology and Antimicrobials vol 15 no1 p 48 2016

[3] L A Barton and M W Simon ldquoProphylactic antibioticsIneffective or inefficaciousrdquo Clinical Pediatrics vol 53 no 8 p813 2014

[4] J Neumaier ldquoAntibiotics are up to 90 ineffective what reallyhelps in common coldsrdquo MMWmdashFortschritte der Medizin vol153 no 3 pp 18-19 2011

BioMed Research International 11

[5] B Schlemmer ldquoBetter prescribing of antibiotics Preventing therisk of ineffective treatment in current infectionrdquo La Revue dupraticien vol 53 no 14 pp 1525-1526 2003

[6] P Stiefelhagen ldquoSuspected severe pneumonia Antibiotics areineffective - what nowrdquo MMWmdashFortschritte der Medizin vol157 no 17 p 28 2015

[7] Z Li and M Knetsch ldquoAntibacterial strategies for wounddressing preventing infection and stimulating healingrdquoCurrentPharmaceutical Design vol 24 no 8 pp 936ndash951 2018

[8] W Xu S Dong Y Han S Li and Y Liu ldquoHydrogels asantibacterial biomaterialsrdquo Current Pharmaceutical Design vol24 no 8 pp 843ndash854 2018

[9] ldquoMicrobiology by numbersrdquo Nature Reviews Microbiology vol9 no 9 p 628 2011

[10] J P Pearson E C Pesci and B H Iglewski ldquoRoles of Pseu-domonas aeruginosa las and rhl quorum-sensing systems incontrol of elastase and rhamnolipid biosynthesis genesrdquo Journalof Bacteriology vol 179 no 18 pp 5756ndash5767 1997

[11] C Van Delden E C Pesci J P Pearson and B H IglewskildquoStarvation selection restores elastase and rhamnolipid produc-tion in a Pseudomonas aeruginosa quorum-sensing mutantrdquoInfection and Immunity vol 66 no 9 pp 4499ndash4502 1998

[12] L E Dietrich A Price-Whelan A Petersen M Whiteley andD K Newman ldquoThe phenazine pyocyanin is a terminal sig-nalling factor in the quorum sensing network of Pseudomonasaeruginosardquo Molecular Microbiology vol 61 no 5 pp 1308ndash1321 2006

[13] E C Carnes D M Lopez N P Donegan et al ldquoConfinement-induced quorum sensing of individual Staphylococcus aureusbacteriardquoNature Chemical Biology vol 6 no 1 pp 41ndash45 2010

[14] J M Yarwood D J Bartels E M Volper and E P GreenbergldquoQuorum sensing in staphylococcus aureus biofilmsrdquo Journal ofBacteriology vol 186 no 6 pp 1838ndash1850 2004

[15] M J Eickhoff and B L Bassler ldquoSnapShot bacterial quorumsensingrdquo Cell vol 174 no 5 p 1328e1321 2018

[16] M Schuster D Joseph Sexton S P Diggle and E PeterGreenberg ldquoAcyl-homoserine lactone quorum sensing fromevolution to applicationrdquo Annual Review of Microbiology vol67 pp 43ndash63 2013

[17] MH SturmeMKleerebezem J NakayamaA D AkkermansE E Vaugha andWM DeVos ldquoCell to cell communication byautoinducing peptides in gram-positive bacteriardquo Antonie VanLeeuwenhoek vol 81 no 1ndash4 pp 233ndash243 2002

[18] C S Pereira J A Thompson and K B Xavier ldquoAI-2-mediatedsignalling in bacteriardquo FEMS Microbiology Reviews vol 37 no2 pp 156ndash181 2013

[19] M Yang K Sun L Zhou R Yang Z Zhong and J Zhu ldquoFunctional analysis of three AHL autoinducer synthase genes inMesorhizobium loti reveals the important role of quorum sens-ing in symbiotic nodulation rdquoCanadian Journal ofMicrobiologyvol 55 no 2 pp 210ndash214 2009

[20] A Ivanova K Ivanova and T Tzanov ldquoInhibition of Quorum-Sensing A New Paradigm in Controlling Bacterial Virulenceand Biofilm Formationrdquo in Biotechnological Applications ofQuorum Sensing Inhibitors V C Kalia Ed pp 5ndash10 2018

[21] Y Zeng Y Wang Z Yu and Y Huang ldquoHypersensitiveresponse of plasmid-encoded AHL synthase gene to lifestyleand nutrient by Ensifer adhaerens X097rdquo Frontiers in Microbiol-ogy vol 8 p 1160 2017

[22] A O Shpakov ldquoBacterial autoinducing peptidesrdquo Mikrobi-ologiia vol 78 no 3 pp 291ndash303 2009

[23] G J Lyon J S Wright T W Muir and R P Novick ldquoKeydeterminants of receptor activation in the agr autoinducingpeptides of Staphylococcus aureusrdquoBiochemistry vol 41 no 31pp 10095ndash10104 2002

[24] E J Murray and PWilliams ldquoDetection of agr-type autoinduc-ing peptides produced by staphylococcus aureusrdquo Methods inMolecular Biology vol 1673 pp 89ndash96 2018

[25] M J Martin S Clare D Goulding et al ldquoThe agr locus reg-ulates virulence and colonization genes in clostridium difficile027rdquo Journal of Bacteriology vol 195 no 16 pp 3672ndash3681 2013

[26] S Cheraghi L Pourgholi M Shafaati et al ldquoAnalysis ofvirulence genes and accessory gene regulator ( agr ) typesamong methicillin-resistant Staphylococcus aureus strains inIranrdquo Journal of Global Antimicrobial Resistance vol 10 pp 315ndash320 2017

[27] P Gilot G Lina T Cochard and B Poutrel ldquoAnalysis of thegenetic variability of genes encoding the RNA III-activatingcomponents Agr and TRAP in a population of Staphylococcusaureus strains isolated from cows with mastitisrdquo Journal ofClinical Microbiology vol 40 no 11 pp 4060ndash4067 2002

[28] G Lina S Jarraud G Ji et al ldquoTransmembrane topology andhistidine protein kinase activity of AgrC the agr signal receptorin Staphylococcus aureusrdquoMolecular Microbiology vol 28 no3 pp 655ndash662 1998

[29] M Guo S Gamby Y Zheng and H Sintim ldquoSmall moleculeinhibitors of AI-2 signaling in bacteria state-of-the-art andfuture perspectives for anti-quorum sensing agentsrdquo Interna-tional Journal of Molecular Sciences vol 14 no 9 pp 17694ndash17728 2013

[30] JThompson R Oliveira A Djukovic C Ubeda and K XavierldquoManipulation of the quorum sensing signal AI-2 affects theantibiotic-treated gut microbiotardquo Cell Reports vol 10 no 11pp 1861ndash1871 2015

[31] K R Hardie ldquoAutoinducer 2 activity in Escherichia coli culturesupernatants can be actively reduced despite maintenance of anactive synthase LuxSrdquoMicrobiology vol 149 no 3 pp 715ndash7282003

[32] J Wang F Li and Z Tian ldquoRole of microbiota on lunghomeostasis and diseasesrdquo Science China Life Sciences vol 60no 12 pp 1407ndash1415 2017

[33] K Riedel A Gotschlich M Givskov et al ldquoThe cep quorum-sensing system of Burkholderia cepacia H111 controls biofilmformation and swarming motilityrdquoMicrobiology vol 147 no 9pp 2517ndash2528 2001

[34] J C Linnes H Ma and J D Bryers ldquoGiant extracellular matrixbinding protein expression in staphylococcus epidermidis isregulated by biofilm formation and osmotic pressurerdquo CurrentMicrobiology vol 66 no 6 pp 627ndash633 2013

[35] AM Romanı K Fund J Artigas T Schwartz S Sabater andUObst ldquoRelevance of polymeric matrix enzymes during biofilmformationrdquoMicrobial Ecology vol 56 no 3 pp 427ndash436 2008

[36] I Kanwar A K Sah and P K Suresh ldquoBiofilm-mediatedantibiotic-resistant oral bacterial infections mechanism andcombat strategiesrdquo Current Pharmaceutical Design vol 23 no14 pp 2084ndash2095 2017

[37] S Keelara S Thakur and J Patel ldquoBiofilm formation byenvironmental isolates of Salmonella and their sensitivity tonatural antimicrobialsrdquo Foodborne Pathogens and Disease vol13 no 9 pp 509ndash516 2016

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12 BioMed Research International

concentration in evaluation of antibiotic sensitivity of entero-cocci causing peritonitisrdquo Peritoneal Dialysis International vol27 no 4 pp 464-465 2007

[39] B A Niemira and E B Solomon ldquoSensitivity of planktonicand biofilm-associated salmonella spp to ionizing radiationrdquoApplied andEnvironmentalMicrobiology vol 71 no 5 pp 2732ndash2736 2005

[40] A M Gamage G Shui M R Wenk and K L Chua ldquoN-Octanoylhomoserine lactone signalling mediated by the BpsI-BpsR quorum sensing system plays a major role in biofilmformationofBurkholderia pseudomalleirdquoMicrobiology vol 157no 4 pp 1176ndash1186 2011

[41] S H Hong M Hegde J Kim X Wang A Jayaraman andT K Wood ldquoSynthetic quorum-sensing circuit to controlconsortial biofilm formation and dispersal in a microfluidicdevicerdquo Nature Communications vol 3 p 613 2012

[42] P Sankar Ganesh and V Ravishankar Rai ldquoAttenuation ofquorum-sensing-dependent virulence factors and biofilm for-mation by medicinal plants against antibiotic resistant Pseu-domonas aeruginosardquo Journal of Traditional and Complemen-tary Medicine vol 8 no 1 pp 170ndash177 2018

[43] P Shih ldquoEffects of quorum-sensing deficiency on Pseudomonasaeruginosa biofilm formation and antibiotic resistancerdquo Journalof Antimicrobial Chemotherapy vol 49 no 2 pp 309ndash314

[44] M I Chernukha I A Shaginian IM Romanova G VMaleevand A L Gintsburg ldquoThe role of ldquoquorum sensingrdquo regula-tion system in symbiotic interaction of bacteria Burkholderiacepacia and Pseudomonas aeruginosa during mixed infectionrdquoZhurnalMikrobiologii Epidemiologii Immunobiologii no 4 pp32ndash37 2006

[45] F M Husain I Ahmad A S Al-Thubiani H H AbulreeshI M AlHazza and F Aqil ldquoLeaf extracts of Mangifera indicaL inhibit quorum sensing - Regulated production of virulencefactors and biofilm in test bacteriardquo Frontiers in Microbiologyvol 8 p 727 2017

[46] D G Renter J G Morris J M Sargeant et al ldquoPreva-lence risk factors O serogroups and virulence profiles ofshiga toxinndashproducing bacteria from cattle production environ-mentsrdquo Journal of Food Protection vol 68 no 8 pp 1556ndash15652005

[47] A R Hauser ldquoPseudomonas aeruginosa So many virulencefactors so little timerdquo Critical Care Medicine vol 39 no 9 pp2193-2194 2011

[48] R Le Berre S Nguyen E Nowak et al ldquoRelative contributionof three main virulence factors in Pseudomonas aeruginosapneumoniardquo Critical Care Medicine vol 39 no 9 pp 2113ndash2120 2011

[49] M M Gallardo-Garcia G Sanchez-Espin R Ivanova-Georgieva et al ldquoRelationship between pathogenic clinicaland virulence factors of Staphylococcus aureus in infectiveendocarditis versus uncomplicated bacteremia a case-controlstudyrdquo European Journal of Clinical Microbiology amp InfectiousDiseases vol 35 no 5 pp 821ndash828 2016

[50] F Sabouni S Mahmoudi A Bahador et al ldquoVirulence factorsof staphylococcus aureus isolates in an iranian referral childrenrsquoshospitalrdquo Osong Public Health and Research Perspectives vol 5no 2 pp 96ndash100 2014

[51] H M Aboushleib H M Omar R Abozahra A Elsheredyand K Baraka ldquoCorrelation of quorum sensing and virulencefactors in Pseudomonas aeruginosa isolates in Egyptrdquo TheJournal of Infection in Developing Countries vol 9 no 10 pp1091ndash1099 2015

[52] R T Sturbelle L F Avila T B Roos et al ldquoThe role ofquorum sensing in Escherichia coli (ETEC) virulence factorsrdquoVeterinary Microbiology vol 180 no 3-4 pp 245ndash252 2015

[53] J E Paczkowski S Mukherjee A R McCready et alldquoFlavonoids suppress Pseudomonas aeruginosa Virulencethrough allosteric inhibition of quorum-sensing receptorsrdquoTheJournal of Biological Chemistry vol 292 no 10 pp 4064ndash40762017

[54] L Weng Y Yang Y Zhang and L Wang ldquoA new syntheticligand that activatesQscRand blocks antibiotic-tolerant biofilmformation in Pseudomonas aeruginosardquo Applied Microbiologyand Biotechnology vol 98 no 6 pp 2565ndash2572 2014

[55] Y-X Yang Z-H Xu Y-Q Zhang J Tian L-X Wengand L-H Wang ldquoA new quorum-sensing inhibitor attenuatesvirulence and decreases antibiotic resistance in Pseudomonasaeruginosardquo Journal of Microbiology vol 50 no 6 pp 987ndash9932012

[56] J N Capilato S V Philippi T Reardon et al ldquoDevelopment ofa novel series of non-natural triaryl agonists and antagonists ofthe Pseudomonas aeruginosa LasR quorum sensing receptorrdquoBioorganic amp Medicinal Chemistry vol 25 no 1 pp 153ndash1652017

[57] C T OrsquoLoughlin L C Miller A Siryaporn K Drescher MF Semmelhack and B L Bassler ldquoA quorum-sensing inhibitorblocks Pseudomonas aeruginosa virulence and biofilm forma-tionrdquo Proceedings of the National Acadamy of Sciences of theUnited States of America vol 110 no 44 pp 17981ndash17986 2013

[58] G D Geske J C OrsquoNeill D M Miller M E Mattmannand H E Blackwell ldquoModulation of bacterial quorum sensingwith synthetic ligands systematic evaluation of N-acylatedhomoserine lactones in multiple species and new insights intotheir mechanisms of actionrdquo Journal of the American ChemicalSociety vol 129 no 44 pp 13613ndash13625 2007

[59] B K Khajanchi M L Kirtley S M Brackman A KChopra and B A McCormick ldquoImmunomodulatory and pro-tective roles of quorum-sensing signaling molecules N-acylhomoserine lactones during infection of mice with aeromonashydrophilardquo Infection and Immunity vol 79 no 7 pp 2646ndash2657 2011

[60] H Tomioka C Sano and Y Tatano ldquoHost-directed therapeu-tics against mycobacterial infectionsrdquo Current PharmaceuticalDesign vol 23 no 18 pp 2644ndash2656 2017

[61] M R Parsek D L Val B L Hanzelka J E Cronan Jr and EP Greenberg ldquoAcyl homoserine-lactone quorum-sensing signalgenerationrdquo Proceedings of the National Acadamy of Sciences ofthe United States of America vol 96 no 8 pp 4360ndash4365 1999

[62] MK Yadav SW Park SW Chae and J J Song ldquoSinefungin anatural nucleoside analogue of S-adenosylmethionine inhibitsStreptococcus pneumoniae biofilm growthrdquo BioMed ResearchInternational vol 2014 Article ID 156987 10 pages 2014

[63] M Hentzer and M Givskov ldquoPharmacological inhibition ofquorum sensing for the treatment of chronic bacterial infec-tionsrdquo The Journal of Clinical Investigation vol 112 no 9 pp1300ndash1307 2003

[64] V Singh G B Evans D H Lenz et al ldquoFemtomolar tran-sition state analogue inhibitors of 5rsquo-methylthioadenosineS-adenosylhomocysteine nucleosidase fromEscherichia colirdquoTheJournal of Biological Chemistry vol 280 no 18 pp 18265ndash182732005

[65] A Priyadarshi E E Kim and K Y Hwang ldquo Structuralinsights into Staphylococcus aureus enoyl-ACP reductase (FabI)

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in complex with NADP and triclosan rdquo Proteins StructureFunction and Bioinformatics vol 78 no 2 pp 480ndash486 2010

[66] N Surolia and A Surolia ldquoTriclosan offers protection againstblood stages of malaria by inhibiting enoyl-ACP reductase ofPlasmodium falciparumrdquoNatureMedicine vol 7 no 2 pp 167ndash173 2001

[67] E Krol and A Becker ldquoRhizobial homologs of the fattyacid transporter FadL facilitate perception of long-chainacyl-homoserine lactone signalsrdquo Proceedings of the NationalAcadamy of Sciences of the United States of America vol 111 no29 pp 10702ndash10707 2014

[68] J L Copitch R N Whitehead and M A Webber ldquoPrevalenceof decreased susceptibility to triclosan in Salmonella entericaisolates fromanimals andhumans andassociationwithmultipledrug resistancerdquo International Journal of Antimicrobial Agentsvol 36 no 3 pp 247ndash251 2010

[69] S Lu N Wang S Ma X Hu L Kang and Y Yu ldquoParabensand triclosan in shellfish fromShenzhen coastal waters bioindi-cation of pollution and human health risksrdquo EnvironmentalPollution vol 246 pp 257ndash263 2018

[70] N Huma P Shankar J Kushwah et al ldquoDiversity and poly-morphism in AHL-Lactonase gene (aiiA) of Bacillusrdquo Journalof Microbiology and Biotechnology vol 21 no 10 pp 1001ndash10112011

[71] S Y Park B J Hwang M Shin J Kim H Kim and J LeeldquoN-acylhomoserine lactonase-producingRhodococcussppwithdifferent AHL-degrading activitiesrdquo FEMSMicrobiology Lettersvol 261 no 1 pp 102ndash108 2006

[72] A Guendouze L Plener J Bzdrenga et al ldquoEffect of quo-rum quenching lactonase in clinical isolates of pseudomonasaeruginosa and comparison with quorum sensing inhibitorsrdquoFrontiers in Microbiology vol 8 p 227 2017

[73] S Hraiech J Hiblot J Lafleur et al ldquoInhaled lactonase reducespseudomonas aeruginosa quorum sensing and mortality in ratpneumoniardquo PLoS ONE vol 9 no 10 Article ID e107125 2014

[74] J Y Chow Y Yang S B Tay K L Chua and W S YewldquoDisruption of biofilm formation by the human pathogenacinetobacter baumannii using engineered quorum-quenchinglactonasesrdquoAntimicrobial Agents andChemotherapy vol 58 no3 pp 1802ndash1805 2014

[75] X FanM Liang L Wang R Chen H Li and X Liu ldquoAii810 anovel cold-adapted N-acylhomoserine lactonase discovered inametagenome can strongly attenuate Pseudomonas aeruginosavirulence factors and biofilm formationrdquo Frontiers in Microbiol-ogy vol 8 p 1950 2017

[76] MM Sakr KM AboshanabW F ElkhatibMA Yassien andN AHassouna ldquoOverexpressed recombinant quorumquench-ing lactonase reduces the virulence motility and biofilm for-mationofmultidrug-resistant Pseudomonas aeruginosa clinicalisolatesrdquo Appl Microbiol Biotechnol vol 102 no 24 pp 10613ndash10622 2018

[77] C Schipper C Hornung P Bijtenhoorn M Quitschau SGrond andW R Streit ldquoMetagenome-derived clones encodingtwo novel lactonase family proteins involved in biofilm inhibi-tion in pseudomonas aeruginosardquo Applied and EnvironmentalMicrobiology vol 75 no 1 pp 224ndash233 2008

[78] W Dong J Zhu X Guo et al ldquoCharacterization of AiiKan AHL lactonase from Kurthia huakui LAM0618T and itsapplication in quorum quenching on Pseudomonas aeruginosaPAO1rdquo Scientific Reports vol 8 no 1 p 6013 2018

[79] W Liu C Ran Z Liu et al ldquoEffects of dietary Lactobacillusplantarum and AHL lactonase on the control of Aeromonas

hydrophila infection in tilapiardquoMicrobiologyopen vol 5 no 4pp 687ndash699 2016

[80] M Torres J C Reina J C Fuentes-Monteverde et al ldquoAHL-lactonase expression in three marine emerging pathogenicVibrio spp reduces virulence and mortality in brine shrimp(Artemia salina) and Manila clam (Venerupis philippinarum)rdquoPLoS ONE vol 13 no 4 Article ID e0195176 2018

[81] G Vinoj B Vaseeharan S Thomas A J Spiers and S ShanthildquoQuorum-quenching activity of the AHL-lactonase from bacil-lus licheniformis DAHB1 inhibits vibrio biofilm formation invitro and reduces shrimp intestinal colonisation andmortalityrdquoMarine Biotechnology vol 16 no 6 pp 707ndash715 2014

[82] V C Kalia ldquoIn search of versatile organisms for quorum-sensing inhibitors acyl homoserine lactones (AHL)-acylaseand AHL-lactonaserdquo FEMS Microbiology Letters vol 359 no2 p 143 2014

[83] V B Maisuria and A S Nerurkar ldquoInterference of quorumsensing by Delftia sp VM4 depends on the activity of a noveln-acylhomoserine lactone-acylaserdquo PLoS ONE vol 10 no 9Article ID e0138034 2015

[84] R Mukherji N K Varshney P Panigrahi C Suresh and APrabhune ldquoA new role for penicillin acylases degradation ofacyl homoserine lactone quorum sensing signals by Kluyveracitrophila penicillin G acylaserdquo Enzyme and Microbial Technol-ogy vol 56 pp 1ndash7 2014

[85] C F Sio L G Otten R H Cool et al ldquoQuorum quenchingby an N-acyl-homoserine lactone acylase from Pseudomonasaeruginosa PAO1rdquo Infection and Immunity vol 74 no 3 pp1673ndash1682 2006

[86] K Ivanova M M Fernandes E Mendoza and T TzanovldquoEnzyme multilayer coatings inhibit Pseudomonas aeruginosabiofilm formation on urinary cathetersrdquo Applied Microbiologyand Biotechnology vol 99 no 10 pp 4373ndash4385 2015

[87] N Grover J G Plaks S R Summers G R Chado M J Schurrand J L Kaar ldquoAcylase-containing polyurethane coatings withanti-biofilm activityrdquo Biotechnology and Bioengineering vol 113no 12 pp 2535ndash2543 2016

[88] J Lee I Lee J Nam D S Hwang K-M Yeon and JKim ldquoImmobilization and stabilization of acylase on carboxy-lated polyaniline nanofibers for highly effective antifoulingapplication via quorum quenchingrdquo ACS Applied Materials ampInterfaces vol 9 no 18 pp 15424ndash15432 2017

[89] S Uroz S R Chhabra M Camara P Williams P Ogerand Y Dessaux ldquoN-acylhomoserine lactone quorum-sensingmolecules are modified and degraded by Rhodococcus ery-thropolis W2 by both amidolytic and novel oxidoreductaseactivitiesrdquoMicrobiology vol 151 no 10 pp 3313ndash3322 2005

[90] B Eva and S Maria ldquoMicrobial secondary metabolites asinhibitors of pharmaceutically important transferases and oxi-doreductasesrdquo Ceska Slov Farm vol 61 no 3 pp 107ndash114 2012

[91] P Bijtenhoorn H Mayerhofer J Muller-Dieckmann et alldquoA novel metagenomic Short-Chain dehydrogenasereductaseattenuates pseudomonas Aeruginosa biofilm formation andvirulence on Caenorhabditis elegansrdquo PLoS ONE vol 6 no 10Article ID e26278 2011

[92] J D Wildschut R M Lang J K Voordouw and G Voor-douw ldquoRubredoxin oxygen oxidoreductase enhances survivalof desulfovibrio vulgaris hildenborough under microaerophilicconditionsrdquo Journal of Bacteriology vol 188 no 17 pp 6253ndash6260 2006

14 BioMed Research International

[93] X Zhang S Ou-yang JWang L Liao RWu and JWei ldquoCon-struction of antibacterial surface via layer-by-layer methodrdquoCurrent Pharmaceutical Design vol 24 no 8 pp 926ndash935 2018

[94] C Pustelny A Albers K Buldt-Karentzopoulos et al ldquoDiox-ygenase-mediated quenching of quinolone-dependent quorumsensing in pseudomonas aeruginosardquoChemistry amp Biology vol16 no 12 pp 1259ndash1267 2009

[95] J T Hodgkinson W R Galloway M Welch and DR Spring ldquoMicrowave-assisted preparation of the quorum-sensing molecule 2-heptyl-3-hydroxy-4(1H)-quinolone andstructurally related analogsrdquo Nature Protocols vol 7 no 6 pp1184ndash1192 2012

[96] F Witzgall T Depke M Hoffmann et al ldquoThe alkylquinolonerepertoire of Pseudomonas aeruginosa is linked to structuralflexibility of the fabh-like 2-heptyl-3-hydroxy-4(1H)-quinolone(PQS) biosynthesis enzyme PqsBCrdquo ChemBioChem vol 19 no14 pp 1531ndash1544 2018

[97] L Andresen E Sala V Koiv and A Mae ldquoA role for theRcs phosphorelay in regulating expression of plant cell walldegrading enzymes in Pectobacterium carotovorum subspcarotovorumrdquoMicrobiology vol 156 no 5 pp 1323ndash1334 2010

[98] L Andresen V Koiv T Alamae and A Mae ldquoThe Rcs phos-phorelay modulates the expression of plant cell wall degradingenzymes and virulence in Pectobacterium carotovorum sspcarotovorumrdquo FEMS Microbiology Letters vol 273 no 2 pp229ndash238 2007

[99] R K Gupta S Chhibber and K Harjai ldquoAcyl homoserinelactones from culture supernatants of pseudomonas aeruginosaaccelerate host immunomodulationrdquo PLoS ONE vol 6 no 6Article ID e20860 2011

[100] G F Kaufmann J Park J M Mee R J Ulevitch and KD Janda ldquoThe quorum quenching antibody RS2-1G9 protectsmacrophages from the cytotoxic effects of the Pseudomonasaeruginosa quorum sensing signalling molecule N-3-oxo-dodecanoyl-homoserine lactonerdquo Molecular Immunology vol45 no 9 pp 2710ndash2714 2008

[101] S Koul J Prakash A Mishra and V C Kalia ldquoPotential emer-gence of multi-quorum sensing inhibitor resistant (MQSIR)bacteriardquo Indian Journal of Microbiology vol 56 no 1 pp 1ndash182016

[102] T Praneenararat A G Palmer and H E Blackwell ldquoChemicalmethods to interrogate bacterial quorum sensing pathwaysrdquoOrganicampBiomolecular Chemistry vol 10 no 41 pp 8189ndash81992012

[103] J Park R Jagasia G F Kaufmann et al ldquoInfection controlby antibody disruption of bacterial quorum sensing signalingrdquoChemistry amp Biology vol 14 no 10 pp 1119ndash1127 2007

[104] C Grandclement M Tannieres S Morera Y Dessaux DFaure andM Camara ldquoQuorum quenching role in nature andapplied developmentsrdquo FEMSMicrobiology Reviews vol 40 no1 pp 86ndash116 2016

[105] MHan J GuG F Gao andW J Liu ldquoChina in action nationalstrategies to combat against emerging infectious diseasesrdquoScience China Life Sciences vol 60 no 12 pp 1383ndash1385 2017

[106] J Liu H Yu Y Huang et al ldquoComplete genome sequence ofa novel bacteriophage infecting Bradyrhizobium diazoefficiensUSDA110rdquo Science China Life Sciences vol 61 no 1 pp 118ndash1212018

[107] L D Christensen M van Gennip T H Jakobsen et alldquoSynergistic antibacterial efficacy of early combination treat-ment with tobramycin and quorum-sensing inhibitors against

Pseudomonas aeruginosa in an intraperitoneal foreign-bodyinfection mouse modelrdquo Journal of Antimicrobial Chemother-apy vol 67 no 5 pp 1198ndash1206 2012

[108] J Fong M Yuan T H Jakobsen et al ldquoDisulfide bond-containing ajoene analogues as novel quorum sensinginhibitors of Pseudomonas aeruginosardquo Journal of MedicinalChemistry vol 60 no 1 pp 215ndash227 2017

[109] R Garcıa-Contreras M Martınez-Vazquez N VelazquezGuadarrama et al ldquo Resistance to the quorum-quenchingcompounds brominated furanone C-30 and 5-fluorouracil inPseudomonas aeruginosa clinical isolates rdquo Pathogens and Dis-ease vol 68 no 1 pp 8ndash11 2013

[110] T H Jakobsen S K Bragason R K Phipps et al ldquoFood as asource for quorum sensing inhibitors iberin from horseradishrevealed as a quorum sensing inhibitor of pseudomonas aerug-inosardquo Applied and Environmental Microbiology vol 78 no 7pp 2410ndash2421 2012

[111] A Vadekeetil H Saini S Chhibber and K Harjai ldquo Exploitingthe antivirulence efficacy of an ajoene-ciprofloxacin combina-tion against Pseudomonas aeruginosa biofilm associatedmurineacute pyelonephritis rdquo Biofouling vol 32 no 4 pp 371ndash3822016

[112] S Bahari H Zeighami H Mirshahabi S Roudashti and FHaghi ldquoInhibition of pseudomonas aeruginosa quorum sensingby subinhibitory concentrations of curcumin with gentamicinand azithromycinrdquo Journal of Global Antimicrobial Resistancevol 10 pp 21ndash28 2017

[113] A S Roccaro A R Blanco F Giuliano D Rusciano and VEnea ldquoEpigallocatechin-gallate enhances the activity of tetra-cycline in staphylococci by inhibiting its efflux from bacterialcellsrdquo Antimicrobial Agents and Chemotherapy vol 48 no 6pp 1968ndash1973 2004

[114] C Chu J Deng Y Man and Y Qu ldquoGreen tea extractsepigallocatechin-3-gallate for different treatmentsrdquo BioMedResearch International vol 2017 Article ID 5615647 9 pages2017

[115] A Furiga B Lajoie S El Hage G Baziard and C RoquesldquoImpairment of pseudomonas aeruginosa biofilm resistance toantibiotics by combining the drugs with a new quorum-sensinginhibitorrdquo Antimicrobial Agents and Chemotherapy vol 60 no3 pp 1676ndash1686 2016

[116] Y Inoue N Togashi and H Hamashima ldquoFarnesol-induceddisruption of the staphylococcus aureus cytoplasmic mem-branerdquo Biological and Pharmaceutical Bulletin vol 39 no 5 pp653ndash656 2016

[117] C Kim D Hesek M Lee and S Mobashery ldquoPotentiationof the activity of beta-lactam antibiotics by farnesol and itsderivativesrdquo Bioorganic amp Medicinal Chemistry Letters vol 28no 4 pp 642ndash645 2018

[118] G Brackman P Cos L Maes H J Nelis and T Coenye ldquoQuo-rum sensing inhibitors increase the susceptibility of bacterialbiofilms to antibiotics in vitro and in vivordquoAntimicrobial Agentsand Chemotherapy vol 55 no 6 pp 2655ndash2661 2011

[119] G Brackman K Breyne R De Rycke et al ldquoThe quorum sens-ing inhibitor hamamelitannin increases antibiotic susceptibilityof staphylococcus aureus biofilms by affecting peptidoglycanbiosynthesis and eDNA releaserdquo Scientific Reports vol 6 ArticleID 20321 2016

[120] J M Walz R L Avelar K J Longtine K L Carter L A Mer-mel and S O Heard ldquoAnti-infective external coating of centralvenous catheters A randomized noninferiority trial comparing

BioMed Research International 15

5-fluorouracil with chlorhexidinesilver sulfadiazine in pre-venting catheter colonizationrdquo Critical Care Medicine vol 38no 11 pp 2095ndash2102 2010

[121] C van Delden T Kohler F Brunner-Ferber B Francois JCarlet and J Pechere ldquoAzithromycin to prevent Pseudomonasaeruginosa ventilator-associated pneumonia by inhibition ofquorum sensing a randomized controlled trialrdquo Intensive CareMedicine vol 38 no 7 pp 1118ndash1125 2012

[122] A R Smyth P M Cifelli C A Ortori et al ldquoGarlic asan inhibitor of Pseudomonas aeruginosa quorum sensing incystic fibrosisndasha pilot randomized controlled trialrdquo PediatricPulmonology vol 45 no 4 pp 356ndash362 2010

Hindawiwwwhindawicom

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Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

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Nucleic AcidsJournal of

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Submit your manuscripts atwwwhindawicom

BioMed Research International 3

Table1Stud

iesdemon

stratingthequ

orum

sensing(Q

S)sig

nalin

gdisrup

tionby

receptor

inactiv

ation

Abbreviatio

ns3

-oxo-C

12N

-3-oxodo

decano

yl-C

12A

HL

N-acyl-h

omoserine

lacton

esA

Iautoindu

cerC4

-LHL

butenylh

omoserinelactonesC6

-LHLhexano

ylho

moserinelactonesHSLL-hom

oserinelactonePHLprop

ionylh

omoserinelactones

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

In-vitro

Pseudomonas

aerugin

osa

Flavon

oids

Allo

steric

inhibitio

nof

AI-bind

ing

receptorsLasR

andRh

lR

Alteredtranscrip

tionof

QS-controlledtarget

prom

otersa

ndsupp

resses

virulencefactor

prod

uctio

n[53]

In-vitro

Pseudomonas

aerugin

osaPA

O1

N-decanoyl-L

-hom

oserine

benzylester

Activ

atingq

uorum

sensingcontrolrepressor

Attenu

ated

thea

ctivity

ofprotease

andelastase

swarmingmotility

andbiofi

lmform

ation

[5455]

In-vitro

Cele

gansA

549cells

Pseudomonas

aerugin

osaPA

14Meta-brom

o-thiolacton

eInhibitio

nof

LasR

andRh

lRInhibitedbo

ththep

rodu

ctionof

thev

irulencefactor

pyocyaninandbiofi

lmform

ation

[57]

In-vitro

Pseudomonas

aerugin

osa

AHLligands

A4

4-brom

ophenyl-P

HLB7

4-iodo

PHLC1

0and

3-nitro

PHLC14

Bind

ingto

TraR

LasR

and

LuxR

Strong

lyinhibitedvirulencefactorp

rodu

ction

[58]

In-vitro

Mice

Aeromonas

hydrophila

C4-a

ndC6

-HSLs

3-oxo-C1

2-HSL

Regu

latin

gtheh

ostimmun

ereceptor

Increasedsurvivability

ofinfected

mice

[59]

4 BioMed Research International

42 QS Signals Synthesis Inhibition The acyl-homoserinelactone molecules (AHLs) not only participate in bacterialcommunication but also play roles in conversations witheukaryotic cells AHLs can regulate the signaling pathwaysin epithelial cells and affect the behavior of innate immunecells [59 60] Inhibiting the synthesis of AHLs is a directstrategy to reduce AHL-mediated virulence factors andprevent pathological damage (Table 2) For example studieshave revealed that the sinefungin butyryl-SAM and S-adenosylhomocysteine can attenuate the secretion of QS-mediated virulence factors and prevent the bacterial infectionby inhibiting the AHLs synthesis in Pseudomonas aeruginosa[61ndash63] Singh et al reported that immucillin A and itsderivatives can reduce the AHLs synthesis by inhibiting the5-MTANS-adenosylhomocysteine nucleosidase [64] Thetriclosan has been verified to reduce AHL synthesis byinhibiting the production of enoyl-ACP reductase precursors[65 66] However these agents for AHLs synthesis inhibitionalso block the metabolism of amino acid and fatty acidthat play key roles in bacterial basic nutrition [67] Thefact that triclosan increased the antibiotic-resistance of Pseu-domonas aeruginosa implies selective pressure on bacteriawere triggered by the blocking effects of triclosan on themetabolism of amino acid and fatty acid in the bacteria[68] The triclosan is considered as bioindicator pollutiondue to its potential in causing the drug-resistance of thepathogens and increasing human health risks [69] Thusthe drugs specifically targeting AHLs synthesis inhibitionwithout blocking nutritional metabolisms of bacteria shouldbe developed and identified by sufficient in vitro experimentsbefore their clinical application

43 QS Signals Degradation Degradation of QS signals byenzymes can effectively disrupt the ldquocommunicationrdquo amongthe bacteria without causing any selective pressure to thebacteria The enzymes consist of lactonase acylase oxidore-ductases and 3-Hydroxy-2-methyl-4(1H)-quinolone 2 4-dioxygenase all of which are derived from different bacterialstrains and have been applied for QS signals degradation(Tables 3 and 4)

The AHL lactonase a member of Metallo-120573-lactamasesuperfamily was able to prevent bacterial infection by de-grading AHLs with different length of side chain [70 71]TheAHL lactonases were reported to increase bacterial sensitivityto antibiotics without affecting the growth of Pseudomonasaeruginosa [72 73] and Acinetobacter baumannii [74] TheAHL lactonase also has been applied to block the biofilmformation of Pseudomonas aeruginosa [75ndash77] The AHLlactonase AiiK produced by the engineered Escherichia coliwas revealed to inhibit extracellular proteolytic activity andpyocyanin production of Pseudomonas aeruginosa PAO1[78] In addition synergistic action of AHL lactonase andantibiotics was observed in the mice model infected withPseudomonas aeruginosa that is the drugs containing AHLlactonase can effectively inhibit the spread of skin pathogenswhile minimizing the effective dose of antibiotics The AHLlactonase has also been applied in the fishery industry forinstance Liu et al reported the lactonaseAIO6 supplementedto tilapia was able to prevent the Aeromonas hydrophila

infection [79] Studies reported the lactonase AiiA candecrease the virulence and inhibit biofilm formation ofVibrioparahaemolyticus in shrimps [80 81]

The acylase which was initially found in Variovoraxparadoxus and Ralstonia can block the QS signaling byhydrolyzing the amide bond of AHLs [82ndash84] The acylasewas revealed to decrease the growth of Pseudomonas aerug-inosa ATCC 10145 and PAO1 by 60 [85 86] and has beenwidely applied in humanhealth care for example the acylase-coated device showed a well antibacterial property due to theQS signaling disruption by the acylase [87] The acylase isalso chemically immobilized on some nanomaterials to act asan antifouling agent [88] Undoubtedly these applications ofacylase will greatly reduce the health care cost caused by thespread and colonization of pathogenic bacteria on medicaldevices

Oxidoreductases are enzymes that can affect the AHLsspecificity of homologous intracellular receptors by modi-fying acyl side chains thus interfering with the expressionof QS related virulence genes [89] Previous studies havedemonstrated the secretion of oxidoreductases by bacteriaas a protective mechanism instead of a pathogenic sig-naling [90] The BpiB09 oxidoreductase was reported toinhibit the activation of N-3-oxo-dodecanoyl homoserinelactone (3-oxo-C12-HSL) in the Pseudomonas aeruginosaPAO1 and decrease bacterial motility biofilms formation andpyocyanin secretion [91] Immobilization of oxidoreductaseson the glass surface can inhibit the bacterial biofilm forma-tion and decrease the growth rate of Klebsiella oxytoca andKlebsiella pneumoniae [92 93]

The dioxygenase has been revealed to block the quin-olone signals in the QS system of Pseudomonas aerugi-nosa [94] Dioxygenase can degrade 2-heptyl-3-hydroxy-4 (1H)-quinolone mediated signals and decreases signalingmolecules accumulation in the bacterial milieu thereforereducing the secretion of pyocyanin rhamnolipid and lectinA toxin which protects the host from infective damage [9596]

Together the anti-QS signaling enzymes are promisingalternatives to antibiotics that can be used not only to controlbacterial infection but also to minimize the risk of causingantibiotic-resistant strains However the stability of enzymesin vivo is the most difficult problem for their biomedicalapplications It is of great significance to study and developthe stability of the anti-QS signaling enzymes in vivo QSdegradation by nonpathogenic bacteria is an effective strategyfor QS disruption Pectobacterium carotovorum subsp caro-tovorum is a preferred and commonly used bacterial strainforQS degradation [97]This biological strategy for QS signaldegradation has been applied to prevent plant diseases [98]but has not been applied for human diseases treatment Byexploring novel QS-degradation strains it might be possibleto cure the chronic diseases caused by the antibiotic-resistantpathogens

44 Target Antibodies for QS Blockage Theactivation of AHLand AI-2 signaling can induce programmed cell death byaffecting the hosts immune system [59 99] Kaufmann et

BioMed Research International 5

Table2Stud

iesd

emon

stratingtheQ

Sdisrup

tionby

signalssynthesis

inhibitio

nAb

breviatio

nsA

Iautoindu

cerenoyl-A

CPeno

yl-acylcarrie

rproteinH

SLL

-hom

oserinelactoneP

HL

prop

ionylh

omoserinelactones

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

In-vitroRa

tsStreptococcus

pneumoniaeD

-39

Sinefung

inInhibitio

nof

AI-2synthesis

via

downregulatinglux

SpfsandspeE

expressio

nInhibitedpn

eumococcalbiofilm

grow

thin

vitro

and

middlee

arcolonizatio

nin

vivo

[62]

In-vitro

Pseudomonas

aerugin

osa

Sinefung

inbutyryl-SAM

and

S-adenosylho

mocysteine

Inhibitin

gacyl-H

SLsig

nals

Inhibitedform

ationof

acovalentacylndashenzyme

[61]

In-vitro

Escherich

iacoli

Methylth

io-D

ADMe-

immucillin-A

Dow

nregulating51015840-m

ethylth

ioadenosine

S-adenosyl-hom

ocysteinen

ucleosidase

hydrolyzes

Disr

uptedkeybacterialpathw

ayso

fmethylatio

npo

lyam

ines

ynthesis

methion

ines

alvageand

quorum

sensing

[64]

Mou

sePlasmodium

falciparum

Triclosan

Inhibitin

genoyl-A

CPredu

ctase

Protectedagainstb

lood

stageso

fmalariaenh

anced

elastic

strength

[66]

6 BioMed Research International

Table3Stud

iesd

emon

stratingQSdisrup

tionby

signalsdegradation

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

In-vitro

Pseudomonas

aerugin

osa

Lacton

aseS

soPo

xDegradatio

nof

thea

cyl-h

omoserinelactones

Inhibitedthev

irulenceo

f51clin

icalPaerugino

saiso

latedfro

mdiabeticfoot

ulcersby

decreasin

gthe

secretionof

proteasesa

ndpyocyanin

andbiofi

lmform

ation

[72]

In-vitrorats

Pseudomonas

aerugin

osaPA

O1

Lacton

aseS

soPo

x-1

Degradatio

nof

thea

cyl-h

omoserinelactones

Decreased

lasB

virulenceg

enea

ctivitypyocyanin

synthesisproteolyticactiv

ityand

biofi

lmform

ation

Redu

cedthem

ortalityof

ratswith

acutep

neum

onia

from

75to

20A

ttenu

ated

lung

damageo

fthe

rat

mod

el

[73]

In-vitro

AbaumanniiS1S

2S3

Engineered

lacton

ase

Degradatio

nof

thea

cyl-h

omoserinelactones

Redu

cedtheb

iomasso

fAbaumanniiassociated

biofi

lms

[74]

In-vitro

Pseudomonas

aerugin

osa

Lacton

aseA

ii810

Degradatio

nof

thea

cyl-h

omoserinelactones

Attenu

ated

VirulenceF

actorsandBiofi

lmFo

rmationDegradedN-butyryl-L-hom

oserine

lacton

eand

N-(3-oxod

odecanoyl)-L-ho

moserine

lacton

eby

723and100

[75]

In-vitro

Pseudomonas

aerugin

osa

Overexpressionof

lacton

asee

nzym

eAHL-1

Degradatio

nof

thea

cyl-h

omoserinelactones

Redu

cedthep

roteasepyocyanin

rham

nolip

ids

Inhibitedthea

ctivities

onthes

warmingmotility

and

biofi

lmform

ation

[76]

In-vitro

Pseudomonas

aerugin

osa

NovelLacton

asec

lonedby

bpiB01bpiB0

4Degradatio

nof

the

N-(3-oxoo

ctanoyl)-L-ho

moserinelactone

Inhibitedmotility

andbiofi

lmform

ation

[77]

In-vitro

Pseudomonas

aerugin

osaPA

O1

Lacton

aseA

iiKDegradatio

nof

thea

cyl-h

omoserinelactones

Inhibitedtheb

iofilm

form

ationandattenu

ates

extracellularp

roteolyticactiv

ityandpyocyanin

prod

uctio

n[78]

In-vitro

Pseudomonas

aerugin

osaPA

O1

N-Acyl-H

omoserine

Lacton

eAcylase

PA2385

Degradatio

nof

3-oxo-C1

2-HSL

and

2-heptyl-3-hydroxy-4(1H)-

quinolon

e

Redu

cedprod

uctio

nof

thev

irulencefactorselastase

andpyocyanin

[85]

In-vitroC

elegans

Pseudomonas

aerugin

osaPA

O1

NADP-depend

ent

short-c

hain

dehydrogenaseredu

ctase

(bpiB0

9)

Inactiv

ationof

N-(3-oxo-do

decano

yl)-L-ho

moserinelactone

(3-oxo-C

12-H

SL)

Redu

cedpyocyaninprod

uctio

ndecreasedmotility

poor

biofi

lmform

ationandabsent

paralysis

ofC

elegans

[91]

In-vitroplant

Pseudomonas

aerugin

osaPA

O1

3-hydroxy-2-methyl-4

(1H)-

quinolon

e

Catalyzingthec

onversionof

PQSto

N-octanoylanthranilica

cidandcarbon

mon

oxide

R edu

cedexpressio

nof

theP

QSbiosyntheticgene

pqsA

expressionof

theP

QS-regu

latedvirulence

determ

inantslectin

Apyocyaninand

rham

nolip

ids

andvirulenceinplant

[94]

BioMed Research International 7

Table4Ap

plications

involvingwith

AHLs

degradationby

anti-QSa

gents3-oxo-C1

2N-3-oxodo

decano

yl-H

SLA

HLN-acyl-h

omoserinelactonesC4

-LHLbu

tenylhom

oserinelactones

C6-LHL

hexano

ylho

moserinelactones

Objectiv

esStrains

Anti-Q

Sagents

Target

Effects

Ref

Tilapia

Aeromonas

hydrophila

AHLlacton

aseA

IO6

Degradatio

nof

thea

cyl-h

omoserinelactones

Maintainedthem

icrovilli

leng

thin

theforegut

oftilapiabut

significantly

lowe

rthanthoseo

fthe

control

[79]

Shrim

pandclam

Vibriona

ceae

strains

Deletionof

AHLs

genesin

34marineV

ibrio

naceae

strains

Acyl-hom

oserinelactonesinactivation

Redu

cedvirulencea

ndmortalityof

them

utant

strains

inbrines

hrim

pandManila

clam

[80]

Shrim

pVibrio

parahaem

olyticu

sAHL-lacton

ase

(AiiA

)Degradatio

nof

thea

cyl-h

omoserinelactones

Inhibitedvibrio

biofi

lmdevelopm

entand

attenu

ated

infectionandmortalityRe

duce

vibrio

viablecoun

tsandbiofi

lmdevelopm

entintheintestin

e[81]

Enzymem

ultilayer

coatings

Chromobacteriu

mviolaceum

CECT

5999Pseud

omonas

aerugin

osaAT

CC

10145

Acylasefrom

Aspergillus

melleus

Degradatio

nof

C6-LHL

Inhibited50violaceinprod

uctio

nby

Chromobacteriu

mviolaceum

CECT

5999R

educes

theP

seud

omonas

aerugin

osaAT

CC10145b

iofilm

form

ationun

derstatic

anddynamiccond

ition

s

[86]

Acylase-containing

polyurethane

coatings

Pseudomonas

aerugin

osaAT

CC

10145a

ndPA

O1

Acylasefrom

Aspergillus

melleus

Degradatio

nof

C4-LHL

C6-LHL

and

3-oxo-C1

2-LH

L

Immob

ilizatio

nof

acylaseled

toan

approxim

ately

60redu

ctionin

biofi

lmform

ation

redu

cethe

secretionof

pyocyanin

[87]

Immob

ilizatio

non

Nanofi

bers

Pseudomonas

aerugin

osaPA

O1

Acylase(EC

35114)

Degradatio

nof

AHLindu

cers

Redu

cedtheb

iofilmbiofoulingform

ationun

der

static

andcontinuo

usflo

wcond

ition

s[88]

8 BioMed Research International

Table5Stud

iesd

emon

stratingQSdisrup

tionby

antib

odiestargetin

g

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

In-vitroandRA

W2647cells

Pseudomonas

aerugin

osa

Antibod

yRS2-1G9

generatedagainsta

3-oxo-do

decano

ylho

moserinelactone

analog

hapten

Targetingtheb

acteria

lN-3-oxo-dod

ecanoyl

homoserinelactone

molecules

Protectm

urineb

onem

arrow-derived

macroph

ages

from

thec

ytotoxiceffectsandalso

preventedthe

activ

ationof

them

itogen-activ

ated

proteinkinase

p38

[100]

In-vitro

Pseudomonas

aerugin

osa

Antibod

yXYD

-11G

2Hydrolyzing

N-3-(oxod

odecanoyl)-L-ho

moserine

lacton

eSupp

ressed

QSsig

nalin

g[101]

In-vitroandmou

semod

elStaphylococcus

aureus

Antibod

yAP4

-24H

11elicitedagainsta

ratio

nally

desig

nedhapten

Sequ

estrationof

thea

utoind

ucingp

eptid

e-4

Supp

ressed

Saureus

pathogenicity

inan

abscess

form

ationmou

semod

elin

vivo

andprovided

completep

rotectionagainsta

lethalStaphylococcus

aureus

challenge

[103]

BioMed Research International 9

Table6Stud

iesd

emon

stratingthes

ynergistice

ffectso

fanti-Q

Sagentsandantib

iotic

s

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

Mice

Pseudomonas

aerugin

osa

Furano

neC-

30ajoeneo

rho

rseradish

juicee

xtractin

Com

binatio

ncurcum

in

QSinhibitio

nenhancethe

sensitivity

ofpathogen

toantib

iotic

sRe

sultedin

anincreasedclearanceo

fPseud

omonas

aerugin

osain

aforeign

-bod

yinfectionmod

el

[107]

In-vitro

Pseudomonas

aerugin

osa

with

tobram

ycin

gentam

icin

and

azith

romycin

Indu

cedconcentrations

ofC1

2-ho

moserine

lacton

eand

C4-h

omoserinelactone

Curcum

inshow

edsynergisticeffectswith

azith

romycin

andgentam

icinC

ombinatio

nuse

redu

cedQS-relatedvirulencefactors

Dow

nregulated

QS-relatedgenes

[112]

In-vitro

Staphylococci

Epigallocatechin-3-gallate

with

Tetracyclin

eInhibitio

nof

thea

ctivity

ofTet(K

)pum

pseffl

uxpu

mps

ofad

ifferentclassTet(B

)En

hanced

theb

acteric

idaleffecto

fTetracyclineo

nStaphylococci

[113]

In-vitro

Pseudomonas

aerugin

osa

N-(2-pyrim

idyl)

butanamideC1

1Dow

nregulationof

rhlrhlA

andlasB

genes

Increasedthes

usceptibilityto

antib

iotic

sand

attenu

ated

thep

atho

genicityof

theb

acteriu

m

[115]

In-vitro

Staphylococcus

aureus

(methicillin-resistant

Sau

reus)

Farnesolwith120573-la

ctam

antib

iotic

s

Inhibitio

nof

lipasea

ctivity

anddisrup

tionof

thec

ytop

lasm

icmem

branethrou

ghthe

leakageo

fpotassiu

mions

Attenu

ated

ther

ateo

fgrowth

ofbacteriaand

coun

terin

gub

iquitous120573-la

ctam

resistancein

bacteria

[116117]

In-vitro

Cele

gansG

aller

iamellonellamice

Burkholderia

cenocepacia

Staphylococcus

aureus

Escherich

iacoli

Baicalin

hydrate

cinn

amaldehyde

hamam

elitann

inwith

Tobram

ycinvancomycin

andclindamycin

Inhibitio

nof

biofi

lmform

ation

QSinhibitio

nenhancethe

sensitivity

ofpathogen

toantib

iotic

s

Com

bining

theu

seof

antib

odyandanti-QSagents

increasedsusceptib

ilityof

theb

acteria

tothe

antib

iotic

and

increasedho

stsurvivalrateaft

erinfection

[118]

10 BioMed Research International

al found in their study [100] that the antibody RS2-1G9can bind to 3-oxo-C12-HSL in the extracellular environmentof Pseudomonas aeruginosa thereby attenuating the inflam-matory response of the host XYD-11G2 antibody has beenshown to catalyze the hydrolysis of 3-oxo-C12-HSL signalingthus inhibiting the pyocyanin production by Gram-negativebacteria [101 102] The monoclonal antibody AP4-24H11 wasfound to block the QS signal of Gram-positive Staphylococcusaureus by interfering with AIP IV [103] Another in vivo studyshowed that the antibody AP4-24H11 could significantlyattenuate the tissue necrosis in the infected model [104]Although these monoclonal antibodies have been identifiedto block the QS signaling of pathogenic bacteria (Table 5)their applications for treating bacterial diseases are still in theinitial stage

45 Combinations of Anti-QS Agents and Antibiotics Com-bining use of antibiotic with an anti-QS agent is the mosteffective clinical strategy for the treatment of bacterial dis-eases at present [105 106] Many studies have confirmed thesynergistic effect of antibiotics and anti-QS agents (Table 6)Ajoene furanone c-30 and horseradish extract have beenrevealed to reduce the expression of virulence factors inPseudomonas aeruginosa and make Pseudomonas aeruginosaeasier to be cleared by tobramycin [107ndash111] Another studyhas confirmed the synergistic effects of curcumin gentam-icin and azithromycin on Pseudomonas aeruginosa that isthe expressions of virulence genes were significantly down-regulated by the combining use of curcumin together withgentamicin or azithromycin and the therapeutic doses ofgentamicin and azithromycin were minimized by curcuminsupplementation [112] The anti-QS compounds such asgallocatechin 3-gallate and caffeic acid enhanced therapeuticeffects on Mycoplasma pneumoniae infection by combininguse with tetracycline ciprofloxacin or gentamicin [113 114]N-(2-pyrimidyl) butylamine was confirmed to enhance theantibacterial effect of tobramycin colistin and ciprofloxacinon Pseudomonas aeruginosa [115] Recent studies [116 117]have shown that both farnesol and hamamelitannin canreduce the virulence of Staphylococcus aureus and increasethe sensitivity of Staphylococcus aureus to 120573-lactam antibi-otics Synergistic effects of hamamelitannin baicalin hydratecinnamaldehyde and antibiotics have been demonstrated indifferent infection models [118 119]These findings imply thatcombining use of antibiotics with ant-QS agents has greattherapeutic potential for bacterial diseases

5 Conclusions

Regulating bacterial QS signaling by QS-targeted agents isan effective strategy to control the production of bacte-rial virulence factors and the formation of biofilm Thisnovel nonantibiotic therapy can inhibit the expression ofpathogenic genes prevent infection and reduce the riskof drug resistance of bacterial cells and has been widelyexploited in recent years A large number of studies haveidentified many anti-QS agents to control the pathogenicphenotypes ofmost bacteria and to attenuate the pathological

damage in various animal infection models However mostanti-QS agents are still in the preclinical phase and morehuman clinical trials are warranted to test their practicalfeasibility The results of several existing clinical studies [120ndash122] on anti-QS agents show that compared with antibioticsthe anti-QS compounds may have potential toxicity andtheir therapeutic effect is not as stable as that of antibioticswhich limited their extensive application Combining use ofanti-QS agents with conventional antibiotics can significantlyimprove the efficacy of therapeutic drugs and decrease thecost of human healthcare and is likely to be the mainapplication method of anti-QS agents for bacterial diseasestreatment in the future

Conflicts of Interest

The authors declare that there are no conflicts of interestregarding the publication of this paper

Acknowledgments

The authors are thankful to the China Scholarship Council(CSC) for both financial support and scholarships Theauthors appreciate Dr Ruiqiang Yang at the Nanjing Agri-culture University for his help on this review This workwas supported by the National Natural Science Foundationof China (31472107) the Youth Science Fund Project of theNational Natural Science Foundation of China (31702126)the Chinese Academy of Sciences lsquoHundred Talentrsquo awardthe National Science Foundation for Distinguished YoungScholars of Hunan Province (2016JJ1015) the Postgradu-ate Research and Innovation Project of Hunan Province(CX2017B348) the Hunan Province ldquoHunan Young Scienceand Technology Innovation Talentrdquo Project (2015RS4053)the Hunan Agricultural University Provincial Outstand-ing Doctoral Dissertation Cultivating Fund (YB2017002)and the Open Foundation of Key Laboratory of Agro-ecological Processes in Subtropical Region Institute ofSubtropical Agriculture Chinese Academy of Sciences(ISA2016101)

References

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[2] F E Akram T El-Tayeb K Abou-Aisha and M El-AzizildquoA combination of silver nanoparticles and visible blue lightenhances the antibacterial efficacy of ineffective antibioticsagainst methicillin-resistant Staphylococcus aureus (MRSA)rdquoAnnals of Clinical Microbiology and Antimicrobials vol 15 no1 p 48 2016

[3] L A Barton and M W Simon ldquoProphylactic antibioticsIneffective or inefficaciousrdquo Clinical Pediatrics vol 53 no 8 p813 2014

[4] J Neumaier ldquoAntibiotics are up to 90 ineffective what reallyhelps in common coldsrdquo MMWmdashFortschritte der Medizin vol153 no 3 pp 18-19 2011

BioMed Research International 11

[5] B Schlemmer ldquoBetter prescribing of antibiotics Preventing therisk of ineffective treatment in current infectionrdquo La Revue dupraticien vol 53 no 14 pp 1525-1526 2003

[6] P Stiefelhagen ldquoSuspected severe pneumonia Antibiotics areineffective - what nowrdquo MMWmdashFortschritte der Medizin vol157 no 17 p 28 2015

[7] Z Li and M Knetsch ldquoAntibacterial strategies for wounddressing preventing infection and stimulating healingrdquoCurrentPharmaceutical Design vol 24 no 8 pp 936ndash951 2018

[8] W Xu S Dong Y Han S Li and Y Liu ldquoHydrogels asantibacterial biomaterialsrdquo Current Pharmaceutical Design vol24 no 8 pp 843ndash854 2018

[9] ldquoMicrobiology by numbersrdquo Nature Reviews Microbiology vol9 no 9 p 628 2011

[10] J P Pearson E C Pesci and B H Iglewski ldquoRoles of Pseu-domonas aeruginosa las and rhl quorum-sensing systems incontrol of elastase and rhamnolipid biosynthesis genesrdquo Journalof Bacteriology vol 179 no 18 pp 5756ndash5767 1997

[11] C Van Delden E C Pesci J P Pearson and B H IglewskildquoStarvation selection restores elastase and rhamnolipid produc-tion in a Pseudomonas aeruginosa quorum-sensing mutantrdquoInfection and Immunity vol 66 no 9 pp 4499ndash4502 1998

[12] L E Dietrich A Price-Whelan A Petersen M Whiteley andD K Newman ldquoThe phenazine pyocyanin is a terminal sig-nalling factor in the quorum sensing network of Pseudomonasaeruginosardquo Molecular Microbiology vol 61 no 5 pp 1308ndash1321 2006

[13] E C Carnes D M Lopez N P Donegan et al ldquoConfinement-induced quorum sensing of individual Staphylococcus aureusbacteriardquoNature Chemical Biology vol 6 no 1 pp 41ndash45 2010

[14] J M Yarwood D J Bartels E M Volper and E P GreenbergldquoQuorum sensing in staphylococcus aureus biofilmsrdquo Journal ofBacteriology vol 186 no 6 pp 1838ndash1850 2004

[15] M J Eickhoff and B L Bassler ldquoSnapShot bacterial quorumsensingrdquo Cell vol 174 no 5 p 1328e1321 2018

[16] M Schuster D Joseph Sexton S P Diggle and E PeterGreenberg ldquoAcyl-homoserine lactone quorum sensing fromevolution to applicationrdquo Annual Review of Microbiology vol67 pp 43ndash63 2013

[17] MH SturmeMKleerebezem J NakayamaA D AkkermansE E Vaugha andWM DeVos ldquoCell to cell communication byautoinducing peptides in gram-positive bacteriardquo Antonie VanLeeuwenhoek vol 81 no 1ndash4 pp 233ndash243 2002

[18] C S Pereira J A Thompson and K B Xavier ldquoAI-2-mediatedsignalling in bacteriardquo FEMS Microbiology Reviews vol 37 no2 pp 156ndash181 2013

[19] M Yang K Sun L Zhou R Yang Z Zhong and J Zhu ldquoFunctional analysis of three AHL autoinducer synthase genes inMesorhizobium loti reveals the important role of quorum sens-ing in symbiotic nodulation rdquoCanadian Journal ofMicrobiologyvol 55 no 2 pp 210ndash214 2009

[20] A Ivanova K Ivanova and T Tzanov ldquoInhibition of Quorum-Sensing A New Paradigm in Controlling Bacterial Virulenceand Biofilm Formationrdquo in Biotechnological Applications ofQuorum Sensing Inhibitors V C Kalia Ed pp 5ndash10 2018

[21] Y Zeng Y Wang Z Yu and Y Huang ldquoHypersensitiveresponse of plasmid-encoded AHL synthase gene to lifestyleand nutrient by Ensifer adhaerens X097rdquo Frontiers in Microbiol-ogy vol 8 p 1160 2017

[22] A O Shpakov ldquoBacterial autoinducing peptidesrdquo Mikrobi-ologiia vol 78 no 3 pp 291ndash303 2009

[23] G J Lyon J S Wright T W Muir and R P Novick ldquoKeydeterminants of receptor activation in the agr autoinducingpeptides of Staphylococcus aureusrdquoBiochemistry vol 41 no 31pp 10095ndash10104 2002

[24] E J Murray and PWilliams ldquoDetection of agr-type autoinduc-ing peptides produced by staphylococcus aureusrdquo Methods inMolecular Biology vol 1673 pp 89ndash96 2018

[25] M J Martin S Clare D Goulding et al ldquoThe agr locus reg-ulates virulence and colonization genes in clostridium difficile027rdquo Journal of Bacteriology vol 195 no 16 pp 3672ndash3681 2013

[26] S Cheraghi L Pourgholi M Shafaati et al ldquoAnalysis ofvirulence genes and accessory gene regulator ( agr ) typesamong methicillin-resistant Staphylococcus aureus strains inIranrdquo Journal of Global Antimicrobial Resistance vol 10 pp 315ndash320 2017

[27] P Gilot G Lina T Cochard and B Poutrel ldquoAnalysis of thegenetic variability of genes encoding the RNA III-activatingcomponents Agr and TRAP in a population of Staphylococcusaureus strains isolated from cows with mastitisrdquo Journal ofClinical Microbiology vol 40 no 11 pp 4060ndash4067 2002

[28] G Lina S Jarraud G Ji et al ldquoTransmembrane topology andhistidine protein kinase activity of AgrC the agr signal receptorin Staphylococcus aureusrdquoMolecular Microbiology vol 28 no3 pp 655ndash662 1998

[29] M Guo S Gamby Y Zheng and H Sintim ldquoSmall moleculeinhibitors of AI-2 signaling in bacteria state-of-the-art andfuture perspectives for anti-quorum sensing agentsrdquo Interna-tional Journal of Molecular Sciences vol 14 no 9 pp 17694ndash17728 2013

[30] JThompson R Oliveira A Djukovic C Ubeda and K XavierldquoManipulation of the quorum sensing signal AI-2 affects theantibiotic-treated gut microbiotardquo Cell Reports vol 10 no 11pp 1861ndash1871 2015

[31] K R Hardie ldquoAutoinducer 2 activity in Escherichia coli culturesupernatants can be actively reduced despite maintenance of anactive synthase LuxSrdquoMicrobiology vol 149 no 3 pp 715ndash7282003

[32] J Wang F Li and Z Tian ldquoRole of microbiota on lunghomeostasis and diseasesrdquo Science China Life Sciences vol 60no 12 pp 1407ndash1415 2017

[33] K Riedel A Gotschlich M Givskov et al ldquoThe cep quorum-sensing system of Burkholderia cepacia H111 controls biofilmformation and swarming motilityrdquoMicrobiology vol 147 no 9pp 2517ndash2528 2001

[34] J C Linnes H Ma and J D Bryers ldquoGiant extracellular matrixbinding protein expression in staphylococcus epidermidis isregulated by biofilm formation and osmotic pressurerdquo CurrentMicrobiology vol 66 no 6 pp 627ndash633 2013

[35] AM Romanı K Fund J Artigas T Schwartz S Sabater andUObst ldquoRelevance of polymeric matrix enzymes during biofilmformationrdquoMicrobial Ecology vol 56 no 3 pp 427ndash436 2008

[36] I Kanwar A K Sah and P K Suresh ldquoBiofilm-mediatedantibiotic-resistant oral bacterial infections mechanism andcombat strategiesrdquo Current Pharmaceutical Design vol 23 no14 pp 2084ndash2095 2017

[37] S Keelara S Thakur and J Patel ldquoBiofilm formation byenvironmental isolates of Salmonella and their sensitivity tonatural antimicrobialsrdquo Foodborne Pathogens and Disease vol13 no 9 pp 509ndash516 2016

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12 BioMed Research International

concentration in evaluation of antibiotic sensitivity of entero-cocci causing peritonitisrdquo Peritoneal Dialysis International vol27 no 4 pp 464-465 2007

[39] B A Niemira and E B Solomon ldquoSensitivity of planktonicand biofilm-associated salmonella spp to ionizing radiationrdquoApplied andEnvironmentalMicrobiology vol 71 no 5 pp 2732ndash2736 2005

[40] A M Gamage G Shui M R Wenk and K L Chua ldquoN-Octanoylhomoserine lactone signalling mediated by the BpsI-BpsR quorum sensing system plays a major role in biofilmformationofBurkholderia pseudomalleirdquoMicrobiology vol 157no 4 pp 1176ndash1186 2011

[41] S H Hong M Hegde J Kim X Wang A Jayaraman andT K Wood ldquoSynthetic quorum-sensing circuit to controlconsortial biofilm formation and dispersal in a microfluidicdevicerdquo Nature Communications vol 3 p 613 2012

[42] P Sankar Ganesh and V Ravishankar Rai ldquoAttenuation ofquorum-sensing-dependent virulence factors and biofilm for-mation by medicinal plants against antibiotic resistant Pseu-domonas aeruginosardquo Journal of Traditional and Complemen-tary Medicine vol 8 no 1 pp 170ndash177 2018

[43] P Shih ldquoEffects of quorum-sensing deficiency on Pseudomonasaeruginosa biofilm formation and antibiotic resistancerdquo Journalof Antimicrobial Chemotherapy vol 49 no 2 pp 309ndash314

[44] M I Chernukha I A Shaginian IM Romanova G VMaleevand A L Gintsburg ldquoThe role of ldquoquorum sensingrdquo regula-tion system in symbiotic interaction of bacteria Burkholderiacepacia and Pseudomonas aeruginosa during mixed infectionrdquoZhurnalMikrobiologii Epidemiologii Immunobiologii no 4 pp32ndash37 2006

[45] F M Husain I Ahmad A S Al-Thubiani H H AbulreeshI M AlHazza and F Aqil ldquoLeaf extracts of Mangifera indicaL inhibit quorum sensing - Regulated production of virulencefactors and biofilm in test bacteriardquo Frontiers in Microbiologyvol 8 p 727 2017

[46] D G Renter J G Morris J M Sargeant et al ldquoPreva-lence risk factors O serogroups and virulence profiles ofshiga toxinndashproducing bacteria from cattle production environ-mentsrdquo Journal of Food Protection vol 68 no 8 pp 1556ndash15652005

[47] A R Hauser ldquoPseudomonas aeruginosa So many virulencefactors so little timerdquo Critical Care Medicine vol 39 no 9 pp2193-2194 2011

[48] R Le Berre S Nguyen E Nowak et al ldquoRelative contributionof three main virulence factors in Pseudomonas aeruginosapneumoniardquo Critical Care Medicine vol 39 no 9 pp 2113ndash2120 2011

[49] M M Gallardo-Garcia G Sanchez-Espin R Ivanova-Georgieva et al ldquoRelationship between pathogenic clinicaland virulence factors of Staphylococcus aureus in infectiveendocarditis versus uncomplicated bacteremia a case-controlstudyrdquo European Journal of Clinical Microbiology amp InfectiousDiseases vol 35 no 5 pp 821ndash828 2016

[50] F Sabouni S Mahmoudi A Bahador et al ldquoVirulence factorsof staphylococcus aureus isolates in an iranian referral childrenrsquoshospitalrdquo Osong Public Health and Research Perspectives vol 5no 2 pp 96ndash100 2014

[51] H M Aboushleib H M Omar R Abozahra A Elsheredyand K Baraka ldquoCorrelation of quorum sensing and virulencefactors in Pseudomonas aeruginosa isolates in Egyptrdquo TheJournal of Infection in Developing Countries vol 9 no 10 pp1091ndash1099 2015

[52] R T Sturbelle L F Avila T B Roos et al ldquoThe role ofquorum sensing in Escherichia coli (ETEC) virulence factorsrdquoVeterinary Microbiology vol 180 no 3-4 pp 245ndash252 2015

[53] J E Paczkowski S Mukherjee A R McCready et alldquoFlavonoids suppress Pseudomonas aeruginosa Virulencethrough allosteric inhibition of quorum-sensing receptorsrdquoTheJournal of Biological Chemistry vol 292 no 10 pp 4064ndash40762017

[54] L Weng Y Yang Y Zhang and L Wang ldquoA new syntheticligand that activatesQscRand blocks antibiotic-tolerant biofilmformation in Pseudomonas aeruginosardquo Applied Microbiologyand Biotechnology vol 98 no 6 pp 2565ndash2572 2014

[55] Y-X Yang Z-H Xu Y-Q Zhang J Tian L-X Wengand L-H Wang ldquoA new quorum-sensing inhibitor attenuatesvirulence and decreases antibiotic resistance in Pseudomonasaeruginosardquo Journal of Microbiology vol 50 no 6 pp 987ndash9932012

[56] J N Capilato S V Philippi T Reardon et al ldquoDevelopment ofa novel series of non-natural triaryl agonists and antagonists ofthe Pseudomonas aeruginosa LasR quorum sensing receptorrdquoBioorganic amp Medicinal Chemistry vol 25 no 1 pp 153ndash1652017

[57] C T OrsquoLoughlin L C Miller A Siryaporn K Drescher MF Semmelhack and B L Bassler ldquoA quorum-sensing inhibitorblocks Pseudomonas aeruginosa virulence and biofilm forma-tionrdquo Proceedings of the National Acadamy of Sciences of theUnited States of America vol 110 no 44 pp 17981ndash17986 2013

[58] G D Geske J C OrsquoNeill D M Miller M E Mattmannand H E Blackwell ldquoModulation of bacterial quorum sensingwith synthetic ligands systematic evaluation of N-acylatedhomoserine lactones in multiple species and new insights intotheir mechanisms of actionrdquo Journal of the American ChemicalSociety vol 129 no 44 pp 13613ndash13625 2007

[59] B K Khajanchi M L Kirtley S M Brackman A KChopra and B A McCormick ldquoImmunomodulatory and pro-tective roles of quorum-sensing signaling molecules N-acylhomoserine lactones during infection of mice with aeromonashydrophilardquo Infection and Immunity vol 79 no 7 pp 2646ndash2657 2011

[60] H Tomioka C Sano and Y Tatano ldquoHost-directed therapeu-tics against mycobacterial infectionsrdquo Current PharmaceuticalDesign vol 23 no 18 pp 2644ndash2656 2017

[61] M R Parsek D L Val B L Hanzelka J E Cronan Jr and EP Greenberg ldquoAcyl homoserine-lactone quorum-sensing signalgenerationrdquo Proceedings of the National Acadamy of Sciences ofthe United States of America vol 96 no 8 pp 4360ndash4365 1999

[62] MK Yadav SW Park SW Chae and J J Song ldquoSinefungin anatural nucleoside analogue of S-adenosylmethionine inhibitsStreptococcus pneumoniae biofilm growthrdquo BioMed ResearchInternational vol 2014 Article ID 156987 10 pages 2014

[63] M Hentzer and M Givskov ldquoPharmacological inhibition ofquorum sensing for the treatment of chronic bacterial infec-tionsrdquo The Journal of Clinical Investigation vol 112 no 9 pp1300ndash1307 2003

[64] V Singh G B Evans D H Lenz et al ldquoFemtomolar tran-sition state analogue inhibitors of 5rsquo-methylthioadenosineS-adenosylhomocysteine nucleosidase fromEscherichia colirdquoTheJournal of Biological Chemistry vol 280 no 18 pp 18265ndash182732005

[65] A Priyadarshi E E Kim and K Y Hwang ldquo Structuralinsights into Staphylococcus aureus enoyl-ACP reductase (FabI)

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in complex with NADP and triclosan rdquo Proteins StructureFunction and Bioinformatics vol 78 no 2 pp 480ndash486 2010

[66] N Surolia and A Surolia ldquoTriclosan offers protection againstblood stages of malaria by inhibiting enoyl-ACP reductase ofPlasmodium falciparumrdquoNatureMedicine vol 7 no 2 pp 167ndash173 2001

[67] E Krol and A Becker ldquoRhizobial homologs of the fattyacid transporter FadL facilitate perception of long-chainacyl-homoserine lactone signalsrdquo Proceedings of the NationalAcadamy of Sciences of the United States of America vol 111 no29 pp 10702ndash10707 2014

[68] J L Copitch R N Whitehead and M A Webber ldquoPrevalenceof decreased susceptibility to triclosan in Salmonella entericaisolates fromanimals andhumans andassociationwithmultipledrug resistancerdquo International Journal of Antimicrobial Agentsvol 36 no 3 pp 247ndash251 2010

[69] S Lu N Wang S Ma X Hu L Kang and Y Yu ldquoParabensand triclosan in shellfish fromShenzhen coastal waters bioindi-cation of pollution and human health risksrdquo EnvironmentalPollution vol 246 pp 257ndash263 2018

[70] N Huma P Shankar J Kushwah et al ldquoDiversity and poly-morphism in AHL-Lactonase gene (aiiA) of Bacillusrdquo Journalof Microbiology and Biotechnology vol 21 no 10 pp 1001ndash10112011

[71] S Y Park B J Hwang M Shin J Kim H Kim and J LeeldquoN-acylhomoserine lactonase-producingRhodococcussppwithdifferent AHL-degrading activitiesrdquo FEMSMicrobiology Lettersvol 261 no 1 pp 102ndash108 2006

[72] A Guendouze L Plener J Bzdrenga et al ldquoEffect of quo-rum quenching lactonase in clinical isolates of pseudomonasaeruginosa and comparison with quorum sensing inhibitorsrdquoFrontiers in Microbiology vol 8 p 227 2017

[73] S Hraiech J Hiblot J Lafleur et al ldquoInhaled lactonase reducespseudomonas aeruginosa quorum sensing and mortality in ratpneumoniardquo PLoS ONE vol 9 no 10 Article ID e107125 2014

[74] J Y Chow Y Yang S B Tay K L Chua and W S YewldquoDisruption of biofilm formation by the human pathogenacinetobacter baumannii using engineered quorum-quenchinglactonasesrdquoAntimicrobial Agents andChemotherapy vol 58 no3 pp 1802ndash1805 2014

[75] X FanM Liang L Wang R Chen H Li and X Liu ldquoAii810 anovel cold-adapted N-acylhomoserine lactonase discovered inametagenome can strongly attenuate Pseudomonas aeruginosavirulence factors and biofilm formationrdquo Frontiers in Microbiol-ogy vol 8 p 1950 2017

[76] MM Sakr KM AboshanabW F ElkhatibMA Yassien andN AHassouna ldquoOverexpressed recombinant quorumquench-ing lactonase reduces the virulence motility and biofilm for-mationofmultidrug-resistant Pseudomonas aeruginosa clinicalisolatesrdquo Appl Microbiol Biotechnol vol 102 no 24 pp 10613ndash10622 2018

[77] C Schipper C Hornung P Bijtenhoorn M Quitschau SGrond andW R Streit ldquoMetagenome-derived clones encodingtwo novel lactonase family proteins involved in biofilm inhibi-tion in pseudomonas aeruginosardquo Applied and EnvironmentalMicrobiology vol 75 no 1 pp 224ndash233 2008

[78] W Dong J Zhu X Guo et al ldquoCharacterization of AiiKan AHL lactonase from Kurthia huakui LAM0618T and itsapplication in quorum quenching on Pseudomonas aeruginosaPAO1rdquo Scientific Reports vol 8 no 1 p 6013 2018

[79] W Liu C Ran Z Liu et al ldquoEffects of dietary Lactobacillusplantarum and AHL lactonase on the control of Aeromonas

hydrophila infection in tilapiardquoMicrobiologyopen vol 5 no 4pp 687ndash699 2016

[80] M Torres J C Reina J C Fuentes-Monteverde et al ldquoAHL-lactonase expression in three marine emerging pathogenicVibrio spp reduces virulence and mortality in brine shrimp(Artemia salina) and Manila clam (Venerupis philippinarum)rdquoPLoS ONE vol 13 no 4 Article ID e0195176 2018

[81] G Vinoj B Vaseeharan S Thomas A J Spiers and S ShanthildquoQuorum-quenching activity of the AHL-lactonase from bacil-lus licheniformis DAHB1 inhibits vibrio biofilm formation invitro and reduces shrimp intestinal colonisation andmortalityrdquoMarine Biotechnology vol 16 no 6 pp 707ndash715 2014

[82] V C Kalia ldquoIn search of versatile organisms for quorum-sensing inhibitors acyl homoserine lactones (AHL)-acylaseand AHL-lactonaserdquo FEMS Microbiology Letters vol 359 no2 p 143 2014

[83] V B Maisuria and A S Nerurkar ldquoInterference of quorumsensing by Delftia sp VM4 depends on the activity of a noveln-acylhomoserine lactone-acylaserdquo PLoS ONE vol 10 no 9Article ID e0138034 2015

[84] R Mukherji N K Varshney P Panigrahi C Suresh and APrabhune ldquoA new role for penicillin acylases degradation ofacyl homoserine lactone quorum sensing signals by Kluyveracitrophila penicillin G acylaserdquo Enzyme and Microbial Technol-ogy vol 56 pp 1ndash7 2014

[85] C F Sio L G Otten R H Cool et al ldquoQuorum quenchingby an N-acyl-homoserine lactone acylase from Pseudomonasaeruginosa PAO1rdquo Infection and Immunity vol 74 no 3 pp1673ndash1682 2006

[86] K Ivanova M M Fernandes E Mendoza and T TzanovldquoEnzyme multilayer coatings inhibit Pseudomonas aeruginosabiofilm formation on urinary cathetersrdquo Applied Microbiologyand Biotechnology vol 99 no 10 pp 4373ndash4385 2015

[87] N Grover J G Plaks S R Summers G R Chado M J Schurrand J L Kaar ldquoAcylase-containing polyurethane coatings withanti-biofilm activityrdquo Biotechnology and Bioengineering vol 113no 12 pp 2535ndash2543 2016

[88] J Lee I Lee J Nam D S Hwang K-M Yeon and JKim ldquoImmobilization and stabilization of acylase on carboxy-lated polyaniline nanofibers for highly effective antifoulingapplication via quorum quenchingrdquo ACS Applied Materials ampInterfaces vol 9 no 18 pp 15424ndash15432 2017

[89] S Uroz S R Chhabra M Camara P Williams P Ogerand Y Dessaux ldquoN-acylhomoserine lactone quorum-sensingmolecules are modified and degraded by Rhodococcus ery-thropolis W2 by both amidolytic and novel oxidoreductaseactivitiesrdquoMicrobiology vol 151 no 10 pp 3313ndash3322 2005

[90] B Eva and S Maria ldquoMicrobial secondary metabolites asinhibitors of pharmaceutically important transferases and oxi-doreductasesrdquo Ceska Slov Farm vol 61 no 3 pp 107ndash114 2012

[91] P Bijtenhoorn H Mayerhofer J Muller-Dieckmann et alldquoA novel metagenomic Short-Chain dehydrogenasereductaseattenuates pseudomonas Aeruginosa biofilm formation andvirulence on Caenorhabditis elegansrdquo PLoS ONE vol 6 no 10Article ID e26278 2011

[92] J D Wildschut R M Lang J K Voordouw and G Voor-douw ldquoRubredoxin oxygen oxidoreductase enhances survivalof desulfovibrio vulgaris hildenborough under microaerophilicconditionsrdquo Journal of Bacteriology vol 188 no 17 pp 6253ndash6260 2006

14 BioMed Research International

[93] X Zhang S Ou-yang JWang L Liao RWu and JWei ldquoCon-struction of antibacterial surface via layer-by-layer methodrdquoCurrent Pharmaceutical Design vol 24 no 8 pp 926ndash935 2018

[94] C Pustelny A Albers K Buldt-Karentzopoulos et al ldquoDiox-ygenase-mediated quenching of quinolone-dependent quorumsensing in pseudomonas aeruginosardquoChemistry amp Biology vol16 no 12 pp 1259ndash1267 2009

[95] J T Hodgkinson W R Galloway M Welch and DR Spring ldquoMicrowave-assisted preparation of the quorum-sensing molecule 2-heptyl-3-hydroxy-4(1H)-quinolone andstructurally related analogsrdquo Nature Protocols vol 7 no 6 pp1184ndash1192 2012

[96] F Witzgall T Depke M Hoffmann et al ldquoThe alkylquinolonerepertoire of Pseudomonas aeruginosa is linked to structuralflexibility of the fabh-like 2-heptyl-3-hydroxy-4(1H)-quinolone(PQS) biosynthesis enzyme PqsBCrdquo ChemBioChem vol 19 no14 pp 1531ndash1544 2018

[97] L Andresen E Sala V Koiv and A Mae ldquoA role for theRcs phosphorelay in regulating expression of plant cell walldegrading enzymes in Pectobacterium carotovorum subspcarotovorumrdquoMicrobiology vol 156 no 5 pp 1323ndash1334 2010

[98] L Andresen V Koiv T Alamae and A Mae ldquoThe Rcs phos-phorelay modulates the expression of plant cell wall degradingenzymes and virulence in Pectobacterium carotovorum sspcarotovorumrdquo FEMS Microbiology Letters vol 273 no 2 pp229ndash238 2007

[99] R K Gupta S Chhibber and K Harjai ldquoAcyl homoserinelactones from culture supernatants of pseudomonas aeruginosaaccelerate host immunomodulationrdquo PLoS ONE vol 6 no 6Article ID e20860 2011

[100] G F Kaufmann J Park J M Mee R J Ulevitch and KD Janda ldquoThe quorum quenching antibody RS2-1G9 protectsmacrophages from the cytotoxic effects of the Pseudomonasaeruginosa quorum sensing signalling molecule N-3-oxo-dodecanoyl-homoserine lactonerdquo Molecular Immunology vol45 no 9 pp 2710ndash2714 2008

[101] S Koul J Prakash A Mishra and V C Kalia ldquoPotential emer-gence of multi-quorum sensing inhibitor resistant (MQSIR)bacteriardquo Indian Journal of Microbiology vol 56 no 1 pp 1ndash182016

[102] T Praneenararat A G Palmer and H E Blackwell ldquoChemicalmethods to interrogate bacterial quorum sensing pathwaysrdquoOrganicampBiomolecular Chemistry vol 10 no 41 pp 8189ndash81992012

[103] J Park R Jagasia G F Kaufmann et al ldquoInfection controlby antibody disruption of bacterial quorum sensing signalingrdquoChemistry amp Biology vol 14 no 10 pp 1119ndash1127 2007

[104] C Grandclement M Tannieres S Morera Y Dessaux DFaure andM Camara ldquoQuorum quenching role in nature andapplied developmentsrdquo FEMSMicrobiology Reviews vol 40 no1 pp 86ndash116 2016

[105] MHan J GuG F Gao andW J Liu ldquoChina in action nationalstrategies to combat against emerging infectious diseasesrdquoScience China Life Sciences vol 60 no 12 pp 1383ndash1385 2017

[106] J Liu H Yu Y Huang et al ldquoComplete genome sequence ofa novel bacteriophage infecting Bradyrhizobium diazoefficiensUSDA110rdquo Science China Life Sciences vol 61 no 1 pp 118ndash1212018

[107] L D Christensen M van Gennip T H Jakobsen et alldquoSynergistic antibacterial efficacy of early combination treat-ment with tobramycin and quorum-sensing inhibitors against

Pseudomonas aeruginosa in an intraperitoneal foreign-bodyinfection mouse modelrdquo Journal of Antimicrobial Chemother-apy vol 67 no 5 pp 1198ndash1206 2012

[108] J Fong M Yuan T H Jakobsen et al ldquoDisulfide bond-containing ajoene analogues as novel quorum sensinginhibitors of Pseudomonas aeruginosardquo Journal of MedicinalChemistry vol 60 no 1 pp 215ndash227 2017

[109] R Garcıa-Contreras M Martınez-Vazquez N VelazquezGuadarrama et al ldquo Resistance to the quorum-quenchingcompounds brominated furanone C-30 and 5-fluorouracil inPseudomonas aeruginosa clinical isolates rdquo Pathogens and Dis-ease vol 68 no 1 pp 8ndash11 2013

[110] T H Jakobsen S K Bragason R K Phipps et al ldquoFood as asource for quorum sensing inhibitors iberin from horseradishrevealed as a quorum sensing inhibitor of pseudomonas aerug-inosardquo Applied and Environmental Microbiology vol 78 no 7pp 2410ndash2421 2012

[111] A Vadekeetil H Saini S Chhibber and K Harjai ldquo Exploitingthe antivirulence efficacy of an ajoene-ciprofloxacin combina-tion against Pseudomonas aeruginosa biofilm associatedmurineacute pyelonephritis rdquo Biofouling vol 32 no 4 pp 371ndash3822016

[112] S Bahari H Zeighami H Mirshahabi S Roudashti and FHaghi ldquoInhibition of pseudomonas aeruginosa quorum sensingby subinhibitory concentrations of curcumin with gentamicinand azithromycinrdquo Journal of Global Antimicrobial Resistancevol 10 pp 21ndash28 2017

[113] A S Roccaro A R Blanco F Giuliano D Rusciano and VEnea ldquoEpigallocatechin-gallate enhances the activity of tetra-cycline in staphylococci by inhibiting its efflux from bacterialcellsrdquo Antimicrobial Agents and Chemotherapy vol 48 no 6pp 1968ndash1973 2004

[114] C Chu J Deng Y Man and Y Qu ldquoGreen tea extractsepigallocatechin-3-gallate for different treatmentsrdquo BioMedResearch International vol 2017 Article ID 5615647 9 pages2017

[115] A Furiga B Lajoie S El Hage G Baziard and C RoquesldquoImpairment of pseudomonas aeruginosa biofilm resistance toantibiotics by combining the drugs with a new quorum-sensinginhibitorrdquo Antimicrobial Agents and Chemotherapy vol 60 no3 pp 1676ndash1686 2016

[116] Y Inoue N Togashi and H Hamashima ldquoFarnesol-induceddisruption of the staphylococcus aureus cytoplasmic mem-branerdquo Biological and Pharmaceutical Bulletin vol 39 no 5 pp653ndash656 2016

[117] C Kim D Hesek M Lee and S Mobashery ldquoPotentiationof the activity of beta-lactam antibiotics by farnesol and itsderivativesrdquo Bioorganic amp Medicinal Chemistry Letters vol 28no 4 pp 642ndash645 2018

[118] G Brackman P Cos L Maes H J Nelis and T Coenye ldquoQuo-rum sensing inhibitors increase the susceptibility of bacterialbiofilms to antibiotics in vitro and in vivordquoAntimicrobial Agentsand Chemotherapy vol 55 no 6 pp 2655ndash2661 2011

[119] G Brackman K Breyne R De Rycke et al ldquoThe quorum sens-ing inhibitor hamamelitannin increases antibiotic susceptibilityof staphylococcus aureus biofilms by affecting peptidoglycanbiosynthesis and eDNA releaserdquo Scientific Reports vol 6 ArticleID 20321 2016

[120] J M Walz R L Avelar K J Longtine K L Carter L A Mer-mel and S O Heard ldquoAnti-infective external coating of centralvenous catheters A randomized noninferiority trial comparing

BioMed Research International 15

5-fluorouracil with chlorhexidinesilver sulfadiazine in pre-venting catheter colonizationrdquo Critical Care Medicine vol 38no 11 pp 2095ndash2102 2010

[121] C van Delden T Kohler F Brunner-Ferber B Francois JCarlet and J Pechere ldquoAzithromycin to prevent Pseudomonasaeruginosa ventilator-associated pneumonia by inhibition ofquorum sensing a randomized controlled trialrdquo Intensive CareMedicine vol 38 no 7 pp 1118ndash1125 2012

[122] A R Smyth P M Cifelli C A Ortori et al ldquoGarlic asan inhibitor of Pseudomonas aeruginosa quorum sensing incystic fibrosisndasha pilot randomized controlled trialrdquo PediatricPulmonology vol 45 no 4 pp 356ndash362 2010

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4 BioMed Research International

42 QS Signals Synthesis Inhibition The acyl-homoserinelactone molecules (AHLs) not only participate in bacterialcommunication but also play roles in conversations witheukaryotic cells AHLs can regulate the signaling pathwaysin epithelial cells and affect the behavior of innate immunecells [59 60] Inhibiting the synthesis of AHLs is a directstrategy to reduce AHL-mediated virulence factors andprevent pathological damage (Table 2) For example studieshave revealed that the sinefungin butyryl-SAM and S-adenosylhomocysteine can attenuate the secretion of QS-mediated virulence factors and prevent the bacterial infectionby inhibiting the AHLs synthesis in Pseudomonas aeruginosa[61ndash63] Singh et al reported that immucillin A and itsderivatives can reduce the AHLs synthesis by inhibiting the5-MTANS-adenosylhomocysteine nucleosidase [64] Thetriclosan has been verified to reduce AHL synthesis byinhibiting the production of enoyl-ACP reductase precursors[65 66] However these agents for AHLs synthesis inhibitionalso block the metabolism of amino acid and fatty acidthat play key roles in bacterial basic nutrition [67] Thefact that triclosan increased the antibiotic-resistance of Pseu-domonas aeruginosa implies selective pressure on bacteriawere triggered by the blocking effects of triclosan on themetabolism of amino acid and fatty acid in the bacteria[68] The triclosan is considered as bioindicator pollutiondue to its potential in causing the drug-resistance of thepathogens and increasing human health risks [69] Thusthe drugs specifically targeting AHLs synthesis inhibitionwithout blocking nutritional metabolisms of bacteria shouldbe developed and identified by sufficient in vitro experimentsbefore their clinical application

43 QS Signals Degradation Degradation of QS signals byenzymes can effectively disrupt the ldquocommunicationrdquo amongthe bacteria without causing any selective pressure to thebacteria The enzymes consist of lactonase acylase oxidore-ductases and 3-Hydroxy-2-methyl-4(1H)-quinolone 2 4-dioxygenase all of which are derived from different bacterialstrains and have been applied for QS signals degradation(Tables 3 and 4)

The AHL lactonase a member of Metallo-120573-lactamasesuperfamily was able to prevent bacterial infection by de-grading AHLs with different length of side chain [70 71]TheAHL lactonases were reported to increase bacterial sensitivityto antibiotics without affecting the growth of Pseudomonasaeruginosa [72 73] and Acinetobacter baumannii [74] TheAHL lactonase also has been applied to block the biofilmformation of Pseudomonas aeruginosa [75ndash77] The AHLlactonase AiiK produced by the engineered Escherichia coliwas revealed to inhibit extracellular proteolytic activity andpyocyanin production of Pseudomonas aeruginosa PAO1[78] In addition synergistic action of AHL lactonase andantibiotics was observed in the mice model infected withPseudomonas aeruginosa that is the drugs containing AHLlactonase can effectively inhibit the spread of skin pathogenswhile minimizing the effective dose of antibiotics The AHLlactonase has also been applied in the fishery industry forinstance Liu et al reported the lactonaseAIO6 supplementedto tilapia was able to prevent the Aeromonas hydrophila

infection [79] Studies reported the lactonase AiiA candecrease the virulence and inhibit biofilm formation ofVibrioparahaemolyticus in shrimps [80 81]

The acylase which was initially found in Variovoraxparadoxus and Ralstonia can block the QS signaling byhydrolyzing the amide bond of AHLs [82ndash84] The acylasewas revealed to decrease the growth of Pseudomonas aerug-inosa ATCC 10145 and PAO1 by 60 [85 86] and has beenwidely applied in humanhealth care for example the acylase-coated device showed a well antibacterial property due to theQS signaling disruption by the acylase [87] The acylase isalso chemically immobilized on some nanomaterials to act asan antifouling agent [88] Undoubtedly these applications ofacylase will greatly reduce the health care cost caused by thespread and colonization of pathogenic bacteria on medicaldevices

Oxidoreductases are enzymes that can affect the AHLsspecificity of homologous intracellular receptors by modi-fying acyl side chains thus interfering with the expressionof QS related virulence genes [89] Previous studies havedemonstrated the secretion of oxidoreductases by bacteriaas a protective mechanism instead of a pathogenic sig-naling [90] The BpiB09 oxidoreductase was reported toinhibit the activation of N-3-oxo-dodecanoyl homoserinelactone (3-oxo-C12-HSL) in the Pseudomonas aeruginosaPAO1 and decrease bacterial motility biofilms formation andpyocyanin secretion [91] Immobilization of oxidoreductaseson the glass surface can inhibit the bacterial biofilm forma-tion and decrease the growth rate of Klebsiella oxytoca andKlebsiella pneumoniae [92 93]

The dioxygenase has been revealed to block the quin-olone signals in the QS system of Pseudomonas aerugi-nosa [94] Dioxygenase can degrade 2-heptyl-3-hydroxy-4 (1H)-quinolone mediated signals and decreases signalingmolecules accumulation in the bacterial milieu thereforereducing the secretion of pyocyanin rhamnolipid and lectinA toxin which protects the host from infective damage [9596]

Together the anti-QS signaling enzymes are promisingalternatives to antibiotics that can be used not only to controlbacterial infection but also to minimize the risk of causingantibiotic-resistant strains However the stability of enzymesin vivo is the most difficult problem for their biomedicalapplications It is of great significance to study and developthe stability of the anti-QS signaling enzymes in vivo QSdegradation by nonpathogenic bacteria is an effective strategyfor QS disruption Pectobacterium carotovorum subsp caro-tovorum is a preferred and commonly used bacterial strainforQS degradation [97]This biological strategy for QS signaldegradation has been applied to prevent plant diseases [98]but has not been applied for human diseases treatment Byexploring novel QS-degradation strains it might be possibleto cure the chronic diseases caused by the antibiotic-resistantpathogens

44 Target Antibodies for QS Blockage Theactivation of AHLand AI-2 signaling can induce programmed cell death byaffecting the hosts immune system [59 99] Kaufmann et

BioMed Research International 5

Table2Stud

iesd

emon

stratingtheQ

Sdisrup

tionby

signalssynthesis

inhibitio

nAb

breviatio

nsA

Iautoindu

cerenoyl-A

CPeno

yl-acylcarrie

rproteinH

SLL

-hom

oserinelactoneP

HL

prop

ionylh

omoserinelactones

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

In-vitroRa

tsStreptococcus

pneumoniaeD

-39

Sinefung

inInhibitio

nof

AI-2synthesis

via

downregulatinglux

SpfsandspeE

expressio

nInhibitedpn

eumococcalbiofilm

grow

thin

vitro

and

middlee

arcolonizatio

nin

vivo

[62]

In-vitro

Pseudomonas

aerugin

osa

Sinefung

inbutyryl-SAM

and

S-adenosylho

mocysteine

Inhibitin

gacyl-H

SLsig

nals

Inhibitedform

ationof

acovalentacylndashenzyme

[61]

In-vitro

Escherich

iacoli

Methylth

io-D

ADMe-

immucillin-A

Dow

nregulating51015840-m

ethylth

ioadenosine

S-adenosyl-hom

ocysteinen

ucleosidase

hydrolyzes

Disr

uptedkeybacterialpathw

ayso

fmethylatio

npo

lyam

ines

ynthesis

methion

ines

alvageand

quorum

sensing

[64]

Mou

sePlasmodium

falciparum

Triclosan

Inhibitin

genoyl-A

CPredu

ctase

Protectedagainstb

lood

stageso

fmalariaenh

anced

elastic

strength

[66]

6 BioMed Research International

Table3Stud

iesd

emon

stratingQSdisrup

tionby

signalsdegradation

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

In-vitro

Pseudomonas

aerugin

osa

Lacton

aseS

soPo

xDegradatio

nof

thea

cyl-h

omoserinelactones

Inhibitedthev

irulenceo

f51clin

icalPaerugino

saiso

latedfro

mdiabeticfoot

ulcersby

decreasin

gthe

secretionof

proteasesa

ndpyocyanin

andbiofi

lmform

ation

[72]

In-vitrorats

Pseudomonas

aerugin

osaPA

O1

Lacton

aseS

soPo

x-1

Degradatio

nof

thea

cyl-h

omoserinelactones

Decreased

lasB

virulenceg

enea

ctivitypyocyanin

synthesisproteolyticactiv

ityand

biofi

lmform

ation

Redu

cedthem

ortalityof

ratswith

acutep

neum

onia

from

75to

20A

ttenu

ated

lung

damageo

fthe

rat

mod

el

[73]

In-vitro

AbaumanniiS1S

2S3

Engineered

lacton

ase

Degradatio

nof

thea

cyl-h

omoserinelactones

Redu

cedtheb

iomasso

fAbaumanniiassociated

biofi

lms

[74]

In-vitro

Pseudomonas

aerugin

osa

Lacton

aseA

ii810

Degradatio

nof

thea

cyl-h

omoserinelactones

Attenu

ated

VirulenceF

actorsandBiofi

lmFo

rmationDegradedN-butyryl-L-hom

oserine

lacton

eand

N-(3-oxod

odecanoyl)-L-ho

moserine

lacton

eby

723and100

[75]

In-vitro

Pseudomonas

aerugin

osa

Overexpressionof

lacton

asee

nzym

eAHL-1

Degradatio

nof

thea

cyl-h

omoserinelactones

Redu

cedthep

roteasepyocyanin

rham

nolip

ids

Inhibitedthea

ctivities

onthes

warmingmotility

and

biofi

lmform

ation

[76]

In-vitro

Pseudomonas

aerugin

osa

NovelLacton

asec

lonedby

bpiB01bpiB0

4Degradatio

nof

the

N-(3-oxoo

ctanoyl)-L-ho

moserinelactone

Inhibitedmotility

andbiofi

lmform

ation

[77]

In-vitro

Pseudomonas

aerugin

osaPA

O1

Lacton

aseA

iiKDegradatio

nof

thea

cyl-h

omoserinelactones

Inhibitedtheb

iofilm

form

ationandattenu

ates

extracellularp

roteolyticactiv

ityandpyocyanin

prod

uctio

n[78]

In-vitro

Pseudomonas

aerugin

osaPA

O1

N-Acyl-H

omoserine

Lacton

eAcylase

PA2385

Degradatio

nof

3-oxo-C1

2-HSL

and

2-heptyl-3-hydroxy-4(1H)-

quinolon

e

Redu

cedprod

uctio

nof

thev

irulencefactorselastase

andpyocyanin

[85]

In-vitroC

elegans

Pseudomonas

aerugin

osaPA

O1

NADP-depend

ent

short-c

hain

dehydrogenaseredu

ctase

(bpiB0

9)

Inactiv

ationof

N-(3-oxo-do

decano

yl)-L-ho

moserinelactone

(3-oxo-C

12-H

SL)

Redu

cedpyocyaninprod

uctio

ndecreasedmotility

poor

biofi

lmform

ationandabsent

paralysis

ofC

elegans

[91]

In-vitroplant

Pseudomonas

aerugin

osaPA

O1

3-hydroxy-2-methyl-4

(1H)-

quinolon

e

Catalyzingthec

onversionof

PQSto

N-octanoylanthranilica

cidandcarbon

mon

oxide

R edu

cedexpressio

nof

theP

QSbiosyntheticgene

pqsA

expressionof

theP

QS-regu

latedvirulence

determ

inantslectin

Apyocyaninand

rham

nolip

ids

andvirulenceinplant

[94]

BioMed Research International 7

Table4Ap

plications

involvingwith

AHLs

degradationby

anti-QSa

gents3-oxo-C1

2N-3-oxodo

decano

yl-H

SLA

HLN-acyl-h

omoserinelactonesC4

-LHLbu

tenylhom

oserinelactones

C6-LHL

hexano

ylho

moserinelactones

Objectiv

esStrains

Anti-Q

Sagents

Target

Effects

Ref

Tilapia

Aeromonas

hydrophila

AHLlacton

aseA

IO6

Degradatio

nof

thea

cyl-h

omoserinelactones

Maintainedthem

icrovilli

leng

thin

theforegut

oftilapiabut

significantly

lowe

rthanthoseo

fthe

control

[79]

Shrim

pandclam

Vibriona

ceae

strains

Deletionof

AHLs

genesin

34marineV

ibrio

naceae

strains

Acyl-hom

oserinelactonesinactivation

Redu

cedvirulencea

ndmortalityof

them

utant

strains

inbrines

hrim

pandManila

clam

[80]

Shrim

pVibrio

parahaem

olyticu

sAHL-lacton

ase

(AiiA

)Degradatio

nof

thea

cyl-h

omoserinelactones

Inhibitedvibrio

biofi

lmdevelopm

entand

attenu

ated

infectionandmortalityRe

duce

vibrio

viablecoun

tsandbiofi

lmdevelopm

entintheintestin

e[81]

Enzymem

ultilayer

coatings

Chromobacteriu

mviolaceum

CECT

5999Pseud

omonas

aerugin

osaAT

CC

10145

Acylasefrom

Aspergillus

melleus

Degradatio

nof

C6-LHL

Inhibited50violaceinprod

uctio

nby

Chromobacteriu

mviolaceum

CECT

5999R

educes

theP

seud

omonas

aerugin

osaAT

CC10145b

iofilm

form

ationun

derstatic

anddynamiccond

ition

s

[86]

Acylase-containing

polyurethane

coatings

Pseudomonas

aerugin

osaAT

CC

10145a

ndPA

O1

Acylasefrom

Aspergillus

melleus

Degradatio

nof

C4-LHL

C6-LHL

and

3-oxo-C1

2-LH

L

Immob

ilizatio

nof

acylaseled

toan

approxim

ately

60redu

ctionin

biofi

lmform

ation

redu

cethe

secretionof

pyocyanin

[87]

Immob

ilizatio

non

Nanofi

bers

Pseudomonas

aerugin

osaPA

O1

Acylase(EC

35114)

Degradatio

nof

AHLindu

cers

Redu

cedtheb

iofilmbiofoulingform

ationun

der

static

andcontinuo

usflo

wcond

ition

s[88]

8 BioMed Research International

Table5Stud

iesd

emon

stratingQSdisrup

tionby

antib

odiestargetin

g

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

In-vitroandRA

W2647cells

Pseudomonas

aerugin

osa

Antibod

yRS2-1G9

generatedagainsta

3-oxo-do

decano

ylho

moserinelactone

analog

hapten

Targetingtheb

acteria

lN-3-oxo-dod

ecanoyl

homoserinelactone

molecules

Protectm

urineb

onem

arrow-derived

macroph

ages

from

thec

ytotoxiceffectsandalso

preventedthe

activ

ationof

them

itogen-activ

ated

proteinkinase

p38

[100]

In-vitro

Pseudomonas

aerugin

osa

Antibod

yXYD

-11G

2Hydrolyzing

N-3-(oxod

odecanoyl)-L-ho

moserine

lacton

eSupp

ressed

QSsig

nalin

g[101]

In-vitroandmou

semod

elStaphylococcus

aureus

Antibod

yAP4

-24H

11elicitedagainsta

ratio

nally

desig

nedhapten

Sequ

estrationof

thea

utoind

ucingp

eptid

e-4

Supp

ressed

Saureus

pathogenicity

inan

abscess

form

ationmou

semod

elin

vivo

andprovided

completep

rotectionagainsta

lethalStaphylococcus

aureus

challenge

[103]

BioMed Research International 9

Table6Stud

iesd

emon

stratingthes

ynergistice

ffectso

fanti-Q

Sagentsandantib

iotic

s

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

Mice

Pseudomonas

aerugin

osa

Furano

neC-

30ajoeneo

rho

rseradish

juicee

xtractin

Com

binatio

ncurcum

in

QSinhibitio

nenhancethe

sensitivity

ofpathogen

toantib

iotic

sRe

sultedin

anincreasedclearanceo

fPseud

omonas

aerugin

osain

aforeign

-bod

yinfectionmod

el

[107]

In-vitro

Pseudomonas

aerugin

osa

with

tobram

ycin

gentam

icin

and

azith

romycin

Indu

cedconcentrations

ofC1

2-ho

moserine

lacton

eand

C4-h

omoserinelactone

Curcum

inshow

edsynergisticeffectswith

azith

romycin

andgentam

icinC

ombinatio

nuse

redu

cedQS-relatedvirulencefactors

Dow

nregulated

QS-relatedgenes

[112]

In-vitro

Staphylococci

Epigallocatechin-3-gallate

with

Tetracyclin

eInhibitio

nof

thea

ctivity

ofTet(K

)pum

pseffl

uxpu

mps

ofad

ifferentclassTet(B

)En

hanced

theb

acteric

idaleffecto

fTetracyclineo

nStaphylococci

[113]

In-vitro

Pseudomonas

aerugin

osa

N-(2-pyrim

idyl)

butanamideC1

1Dow

nregulationof

rhlrhlA

andlasB

genes

Increasedthes

usceptibilityto

antib

iotic

sand

attenu

ated

thep

atho

genicityof

theb

acteriu

m

[115]

In-vitro

Staphylococcus

aureus

(methicillin-resistant

Sau

reus)

Farnesolwith120573-la

ctam

antib

iotic

s

Inhibitio

nof

lipasea

ctivity

anddisrup

tionof

thec

ytop

lasm

icmem

branethrou

ghthe

leakageo

fpotassiu

mions

Attenu

ated

ther

ateo

fgrowth

ofbacteriaand

coun

terin

gub

iquitous120573-la

ctam

resistancein

bacteria

[116117]

In-vitro

Cele

gansG

aller

iamellonellamice

Burkholderia

cenocepacia

Staphylococcus

aureus

Escherich

iacoli

Baicalin

hydrate

cinn

amaldehyde

hamam

elitann

inwith

Tobram

ycinvancomycin

andclindamycin

Inhibitio

nof

biofi

lmform

ation

QSinhibitio

nenhancethe

sensitivity

ofpathogen

toantib

iotic

s

Com

bining

theu

seof

antib

odyandanti-QSagents

increasedsusceptib

ilityof

theb

acteria

tothe

antib

iotic

and

increasedho

stsurvivalrateaft

erinfection

[118]

10 BioMed Research International

al found in their study [100] that the antibody RS2-1G9can bind to 3-oxo-C12-HSL in the extracellular environmentof Pseudomonas aeruginosa thereby attenuating the inflam-matory response of the host XYD-11G2 antibody has beenshown to catalyze the hydrolysis of 3-oxo-C12-HSL signalingthus inhibiting the pyocyanin production by Gram-negativebacteria [101 102] The monoclonal antibody AP4-24H11 wasfound to block the QS signal of Gram-positive Staphylococcusaureus by interfering with AIP IV [103] Another in vivo studyshowed that the antibody AP4-24H11 could significantlyattenuate the tissue necrosis in the infected model [104]Although these monoclonal antibodies have been identifiedto block the QS signaling of pathogenic bacteria (Table 5)their applications for treating bacterial diseases are still in theinitial stage

45 Combinations of Anti-QS Agents and Antibiotics Com-bining use of antibiotic with an anti-QS agent is the mosteffective clinical strategy for the treatment of bacterial dis-eases at present [105 106] Many studies have confirmed thesynergistic effect of antibiotics and anti-QS agents (Table 6)Ajoene furanone c-30 and horseradish extract have beenrevealed to reduce the expression of virulence factors inPseudomonas aeruginosa and make Pseudomonas aeruginosaeasier to be cleared by tobramycin [107ndash111] Another studyhas confirmed the synergistic effects of curcumin gentam-icin and azithromycin on Pseudomonas aeruginosa that isthe expressions of virulence genes were significantly down-regulated by the combining use of curcumin together withgentamicin or azithromycin and the therapeutic doses ofgentamicin and azithromycin were minimized by curcuminsupplementation [112] The anti-QS compounds such asgallocatechin 3-gallate and caffeic acid enhanced therapeuticeffects on Mycoplasma pneumoniae infection by combininguse with tetracycline ciprofloxacin or gentamicin [113 114]N-(2-pyrimidyl) butylamine was confirmed to enhance theantibacterial effect of tobramycin colistin and ciprofloxacinon Pseudomonas aeruginosa [115] Recent studies [116 117]have shown that both farnesol and hamamelitannin canreduce the virulence of Staphylococcus aureus and increasethe sensitivity of Staphylococcus aureus to 120573-lactam antibi-otics Synergistic effects of hamamelitannin baicalin hydratecinnamaldehyde and antibiotics have been demonstrated indifferent infection models [118 119]These findings imply thatcombining use of antibiotics with ant-QS agents has greattherapeutic potential for bacterial diseases

5 Conclusions

Regulating bacterial QS signaling by QS-targeted agents isan effective strategy to control the production of bacte-rial virulence factors and the formation of biofilm Thisnovel nonantibiotic therapy can inhibit the expression ofpathogenic genes prevent infection and reduce the riskof drug resistance of bacterial cells and has been widelyexploited in recent years A large number of studies haveidentified many anti-QS agents to control the pathogenicphenotypes ofmost bacteria and to attenuate the pathological

damage in various animal infection models However mostanti-QS agents are still in the preclinical phase and morehuman clinical trials are warranted to test their practicalfeasibility The results of several existing clinical studies [120ndash122] on anti-QS agents show that compared with antibioticsthe anti-QS compounds may have potential toxicity andtheir therapeutic effect is not as stable as that of antibioticswhich limited their extensive application Combining use ofanti-QS agents with conventional antibiotics can significantlyimprove the efficacy of therapeutic drugs and decrease thecost of human healthcare and is likely to be the mainapplication method of anti-QS agents for bacterial diseasestreatment in the future

Conflicts of Interest

The authors declare that there are no conflicts of interestregarding the publication of this paper

Acknowledgments

The authors are thankful to the China Scholarship Council(CSC) for both financial support and scholarships Theauthors appreciate Dr Ruiqiang Yang at the Nanjing Agri-culture University for his help on this review This workwas supported by the National Natural Science Foundationof China (31472107) the Youth Science Fund Project of theNational Natural Science Foundation of China (31702126)the Chinese Academy of Sciences lsquoHundred Talentrsquo awardthe National Science Foundation for Distinguished YoungScholars of Hunan Province (2016JJ1015) the Postgradu-ate Research and Innovation Project of Hunan Province(CX2017B348) the Hunan Province ldquoHunan Young Scienceand Technology Innovation Talentrdquo Project (2015RS4053)the Hunan Agricultural University Provincial Outstand-ing Doctoral Dissertation Cultivating Fund (YB2017002)and the Open Foundation of Key Laboratory of Agro-ecological Processes in Subtropical Region Institute ofSubtropical Agriculture Chinese Academy of Sciences(ISA2016101)

References

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[2] F E Akram T El-Tayeb K Abou-Aisha and M El-AzizildquoA combination of silver nanoparticles and visible blue lightenhances the antibacterial efficacy of ineffective antibioticsagainst methicillin-resistant Staphylococcus aureus (MRSA)rdquoAnnals of Clinical Microbiology and Antimicrobials vol 15 no1 p 48 2016

[3] L A Barton and M W Simon ldquoProphylactic antibioticsIneffective or inefficaciousrdquo Clinical Pediatrics vol 53 no 8 p813 2014

[4] J Neumaier ldquoAntibiotics are up to 90 ineffective what reallyhelps in common coldsrdquo MMWmdashFortschritte der Medizin vol153 no 3 pp 18-19 2011

BioMed Research International 11

[5] B Schlemmer ldquoBetter prescribing of antibiotics Preventing therisk of ineffective treatment in current infectionrdquo La Revue dupraticien vol 53 no 14 pp 1525-1526 2003

[6] P Stiefelhagen ldquoSuspected severe pneumonia Antibiotics areineffective - what nowrdquo MMWmdashFortschritte der Medizin vol157 no 17 p 28 2015

[7] Z Li and M Knetsch ldquoAntibacterial strategies for wounddressing preventing infection and stimulating healingrdquoCurrentPharmaceutical Design vol 24 no 8 pp 936ndash951 2018

[8] W Xu S Dong Y Han S Li and Y Liu ldquoHydrogels asantibacterial biomaterialsrdquo Current Pharmaceutical Design vol24 no 8 pp 843ndash854 2018

[9] ldquoMicrobiology by numbersrdquo Nature Reviews Microbiology vol9 no 9 p 628 2011

[10] J P Pearson E C Pesci and B H Iglewski ldquoRoles of Pseu-domonas aeruginosa las and rhl quorum-sensing systems incontrol of elastase and rhamnolipid biosynthesis genesrdquo Journalof Bacteriology vol 179 no 18 pp 5756ndash5767 1997

[11] C Van Delden E C Pesci J P Pearson and B H IglewskildquoStarvation selection restores elastase and rhamnolipid produc-tion in a Pseudomonas aeruginosa quorum-sensing mutantrdquoInfection and Immunity vol 66 no 9 pp 4499ndash4502 1998

[12] L E Dietrich A Price-Whelan A Petersen M Whiteley andD K Newman ldquoThe phenazine pyocyanin is a terminal sig-nalling factor in the quorum sensing network of Pseudomonasaeruginosardquo Molecular Microbiology vol 61 no 5 pp 1308ndash1321 2006

[13] E C Carnes D M Lopez N P Donegan et al ldquoConfinement-induced quorum sensing of individual Staphylococcus aureusbacteriardquoNature Chemical Biology vol 6 no 1 pp 41ndash45 2010

[14] J M Yarwood D J Bartels E M Volper and E P GreenbergldquoQuorum sensing in staphylococcus aureus biofilmsrdquo Journal ofBacteriology vol 186 no 6 pp 1838ndash1850 2004

[15] M J Eickhoff and B L Bassler ldquoSnapShot bacterial quorumsensingrdquo Cell vol 174 no 5 p 1328e1321 2018

[16] M Schuster D Joseph Sexton S P Diggle and E PeterGreenberg ldquoAcyl-homoserine lactone quorum sensing fromevolution to applicationrdquo Annual Review of Microbiology vol67 pp 43ndash63 2013

[17] MH SturmeMKleerebezem J NakayamaA D AkkermansE E Vaugha andWM DeVos ldquoCell to cell communication byautoinducing peptides in gram-positive bacteriardquo Antonie VanLeeuwenhoek vol 81 no 1ndash4 pp 233ndash243 2002

[18] C S Pereira J A Thompson and K B Xavier ldquoAI-2-mediatedsignalling in bacteriardquo FEMS Microbiology Reviews vol 37 no2 pp 156ndash181 2013

[19] M Yang K Sun L Zhou R Yang Z Zhong and J Zhu ldquoFunctional analysis of three AHL autoinducer synthase genes inMesorhizobium loti reveals the important role of quorum sens-ing in symbiotic nodulation rdquoCanadian Journal ofMicrobiologyvol 55 no 2 pp 210ndash214 2009

[20] A Ivanova K Ivanova and T Tzanov ldquoInhibition of Quorum-Sensing A New Paradigm in Controlling Bacterial Virulenceand Biofilm Formationrdquo in Biotechnological Applications ofQuorum Sensing Inhibitors V C Kalia Ed pp 5ndash10 2018

[21] Y Zeng Y Wang Z Yu and Y Huang ldquoHypersensitiveresponse of plasmid-encoded AHL synthase gene to lifestyleand nutrient by Ensifer adhaerens X097rdquo Frontiers in Microbiol-ogy vol 8 p 1160 2017

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[23] G J Lyon J S Wright T W Muir and R P Novick ldquoKeydeterminants of receptor activation in the agr autoinducingpeptides of Staphylococcus aureusrdquoBiochemistry vol 41 no 31pp 10095ndash10104 2002

[24] E J Murray and PWilliams ldquoDetection of agr-type autoinduc-ing peptides produced by staphylococcus aureusrdquo Methods inMolecular Biology vol 1673 pp 89ndash96 2018

[25] M J Martin S Clare D Goulding et al ldquoThe agr locus reg-ulates virulence and colonization genes in clostridium difficile027rdquo Journal of Bacteriology vol 195 no 16 pp 3672ndash3681 2013

[26] S Cheraghi L Pourgholi M Shafaati et al ldquoAnalysis ofvirulence genes and accessory gene regulator ( agr ) typesamong methicillin-resistant Staphylococcus aureus strains inIranrdquo Journal of Global Antimicrobial Resistance vol 10 pp 315ndash320 2017

[27] P Gilot G Lina T Cochard and B Poutrel ldquoAnalysis of thegenetic variability of genes encoding the RNA III-activatingcomponents Agr and TRAP in a population of Staphylococcusaureus strains isolated from cows with mastitisrdquo Journal ofClinical Microbiology vol 40 no 11 pp 4060ndash4067 2002

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[30] JThompson R Oliveira A Djukovic C Ubeda and K XavierldquoManipulation of the quorum sensing signal AI-2 affects theantibiotic-treated gut microbiotardquo Cell Reports vol 10 no 11pp 1861ndash1871 2015

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12 BioMed Research International

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[44] M I Chernukha I A Shaginian IM Romanova G VMaleevand A L Gintsburg ldquoThe role of ldquoquorum sensingrdquo regula-tion system in symbiotic interaction of bacteria Burkholderiacepacia and Pseudomonas aeruginosa during mixed infectionrdquoZhurnalMikrobiologii Epidemiologii Immunobiologii no 4 pp32ndash37 2006

[45] F M Husain I Ahmad A S Al-Thubiani H H AbulreeshI M AlHazza and F Aqil ldquoLeaf extracts of Mangifera indicaL inhibit quorum sensing - Regulated production of virulencefactors and biofilm in test bacteriardquo Frontiers in Microbiologyvol 8 p 727 2017

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[75] X FanM Liang L Wang R Chen H Li and X Liu ldquoAii810 anovel cold-adapted N-acylhomoserine lactonase discovered inametagenome can strongly attenuate Pseudomonas aeruginosavirulence factors and biofilm formationrdquo Frontiers in Microbiol-ogy vol 8 p 1950 2017

[76] MM Sakr KM AboshanabW F ElkhatibMA Yassien andN AHassouna ldquoOverexpressed recombinant quorumquench-ing lactonase reduces the virulence motility and biofilm for-mationofmultidrug-resistant Pseudomonas aeruginosa clinicalisolatesrdquo Appl Microbiol Biotechnol vol 102 no 24 pp 10613ndash10622 2018

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hydrophila infection in tilapiardquoMicrobiologyopen vol 5 no 4pp 687ndash699 2016

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[84] R Mukherji N K Varshney P Panigrahi C Suresh and APrabhune ldquoA new role for penicillin acylases degradation ofacyl homoserine lactone quorum sensing signals by Kluyveracitrophila penicillin G acylaserdquo Enzyme and Microbial Technol-ogy vol 56 pp 1ndash7 2014

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[86] K Ivanova M M Fernandes E Mendoza and T TzanovldquoEnzyme multilayer coatings inhibit Pseudomonas aeruginosabiofilm formation on urinary cathetersrdquo Applied Microbiologyand Biotechnology vol 99 no 10 pp 4373ndash4385 2015

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[88] J Lee I Lee J Nam D S Hwang K-M Yeon and JKim ldquoImmobilization and stabilization of acylase on carboxy-lated polyaniline nanofibers for highly effective antifoulingapplication via quorum quenchingrdquo ACS Applied Materials ampInterfaces vol 9 no 18 pp 15424ndash15432 2017

[89] S Uroz S R Chhabra M Camara P Williams P Ogerand Y Dessaux ldquoN-acylhomoserine lactone quorum-sensingmolecules are modified and degraded by Rhodococcus ery-thropolis W2 by both amidolytic and novel oxidoreductaseactivitiesrdquoMicrobiology vol 151 no 10 pp 3313ndash3322 2005

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[95] J T Hodgkinson W R Galloway M Welch and DR Spring ldquoMicrowave-assisted preparation of the quorum-sensing molecule 2-heptyl-3-hydroxy-4(1H)-quinolone andstructurally related analogsrdquo Nature Protocols vol 7 no 6 pp1184ndash1192 2012

[96] F Witzgall T Depke M Hoffmann et al ldquoThe alkylquinolonerepertoire of Pseudomonas aeruginosa is linked to structuralflexibility of the fabh-like 2-heptyl-3-hydroxy-4(1H)-quinolone(PQS) biosynthesis enzyme PqsBCrdquo ChemBioChem vol 19 no14 pp 1531ndash1544 2018

[97] L Andresen E Sala V Koiv and A Mae ldquoA role for theRcs phosphorelay in regulating expression of plant cell walldegrading enzymes in Pectobacterium carotovorum subspcarotovorumrdquoMicrobiology vol 156 no 5 pp 1323ndash1334 2010

[98] L Andresen V Koiv T Alamae and A Mae ldquoThe Rcs phos-phorelay modulates the expression of plant cell wall degradingenzymes and virulence in Pectobacterium carotovorum sspcarotovorumrdquo FEMS Microbiology Letters vol 273 no 2 pp229ndash238 2007

[99] R K Gupta S Chhibber and K Harjai ldquoAcyl homoserinelactones from culture supernatants of pseudomonas aeruginosaaccelerate host immunomodulationrdquo PLoS ONE vol 6 no 6Article ID e20860 2011

[100] G F Kaufmann J Park J M Mee R J Ulevitch and KD Janda ldquoThe quorum quenching antibody RS2-1G9 protectsmacrophages from the cytotoxic effects of the Pseudomonasaeruginosa quorum sensing signalling molecule N-3-oxo-dodecanoyl-homoserine lactonerdquo Molecular Immunology vol45 no 9 pp 2710ndash2714 2008

[101] S Koul J Prakash A Mishra and V C Kalia ldquoPotential emer-gence of multi-quorum sensing inhibitor resistant (MQSIR)bacteriardquo Indian Journal of Microbiology vol 56 no 1 pp 1ndash182016

[102] T Praneenararat A G Palmer and H E Blackwell ldquoChemicalmethods to interrogate bacterial quorum sensing pathwaysrdquoOrganicampBiomolecular Chemistry vol 10 no 41 pp 8189ndash81992012

[103] J Park R Jagasia G F Kaufmann et al ldquoInfection controlby antibody disruption of bacterial quorum sensing signalingrdquoChemistry amp Biology vol 14 no 10 pp 1119ndash1127 2007

[104] C Grandclement M Tannieres S Morera Y Dessaux DFaure andM Camara ldquoQuorum quenching role in nature andapplied developmentsrdquo FEMSMicrobiology Reviews vol 40 no1 pp 86ndash116 2016

[105] MHan J GuG F Gao andW J Liu ldquoChina in action nationalstrategies to combat against emerging infectious diseasesrdquoScience China Life Sciences vol 60 no 12 pp 1383ndash1385 2017

[106] J Liu H Yu Y Huang et al ldquoComplete genome sequence ofa novel bacteriophage infecting Bradyrhizobium diazoefficiensUSDA110rdquo Science China Life Sciences vol 61 no 1 pp 118ndash1212018

[107] L D Christensen M van Gennip T H Jakobsen et alldquoSynergistic antibacterial efficacy of early combination treat-ment with tobramycin and quorum-sensing inhibitors against

Pseudomonas aeruginosa in an intraperitoneal foreign-bodyinfection mouse modelrdquo Journal of Antimicrobial Chemother-apy vol 67 no 5 pp 1198ndash1206 2012

[108] J Fong M Yuan T H Jakobsen et al ldquoDisulfide bond-containing ajoene analogues as novel quorum sensinginhibitors of Pseudomonas aeruginosardquo Journal of MedicinalChemistry vol 60 no 1 pp 215ndash227 2017

[109] R Garcıa-Contreras M Martınez-Vazquez N VelazquezGuadarrama et al ldquo Resistance to the quorum-quenchingcompounds brominated furanone C-30 and 5-fluorouracil inPseudomonas aeruginosa clinical isolates rdquo Pathogens and Dis-ease vol 68 no 1 pp 8ndash11 2013

[110] T H Jakobsen S K Bragason R K Phipps et al ldquoFood as asource for quorum sensing inhibitors iberin from horseradishrevealed as a quorum sensing inhibitor of pseudomonas aerug-inosardquo Applied and Environmental Microbiology vol 78 no 7pp 2410ndash2421 2012

[111] A Vadekeetil H Saini S Chhibber and K Harjai ldquo Exploitingthe antivirulence efficacy of an ajoene-ciprofloxacin combina-tion against Pseudomonas aeruginosa biofilm associatedmurineacute pyelonephritis rdquo Biofouling vol 32 no 4 pp 371ndash3822016

[112] S Bahari H Zeighami H Mirshahabi S Roudashti and FHaghi ldquoInhibition of pseudomonas aeruginosa quorum sensingby subinhibitory concentrations of curcumin with gentamicinand azithromycinrdquo Journal of Global Antimicrobial Resistancevol 10 pp 21ndash28 2017

[113] A S Roccaro A R Blanco F Giuliano D Rusciano and VEnea ldquoEpigallocatechin-gallate enhances the activity of tetra-cycline in staphylococci by inhibiting its efflux from bacterialcellsrdquo Antimicrobial Agents and Chemotherapy vol 48 no 6pp 1968ndash1973 2004

[114] C Chu J Deng Y Man and Y Qu ldquoGreen tea extractsepigallocatechin-3-gallate for different treatmentsrdquo BioMedResearch International vol 2017 Article ID 5615647 9 pages2017

[115] A Furiga B Lajoie S El Hage G Baziard and C RoquesldquoImpairment of pseudomonas aeruginosa biofilm resistance toantibiotics by combining the drugs with a new quorum-sensinginhibitorrdquo Antimicrobial Agents and Chemotherapy vol 60 no3 pp 1676ndash1686 2016

[116] Y Inoue N Togashi and H Hamashima ldquoFarnesol-induceddisruption of the staphylococcus aureus cytoplasmic mem-branerdquo Biological and Pharmaceutical Bulletin vol 39 no 5 pp653ndash656 2016

[117] C Kim D Hesek M Lee and S Mobashery ldquoPotentiationof the activity of beta-lactam antibiotics by farnesol and itsderivativesrdquo Bioorganic amp Medicinal Chemistry Letters vol 28no 4 pp 642ndash645 2018

[118] G Brackman P Cos L Maes H J Nelis and T Coenye ldquoQuo-rum sensing inhibitors increase the susceptibility of bacterialbiofilms to antibiotics in vitro and in vivordquoAntimicrobial Agentsand Chemotherapy vol 55 no 6 pp 2655ndash2661 2011

[119] G Brackman K Breyne R De Rycke et al ldquoThe quorum sens-ing inhibitor hamamelitannin increases antibiotic susceptibilityof staphylococcus aureus biofilms by affecting peptidoglycanbiosynthesis and eDNA releaserdquo Scientific Reports vol 6 ArticleID 20321 2016

[120] J M Walz R L Avelar K J Longtine K L Carter L A Mer-mel and S O Heard ldquoAnti-infective external coating of centralvenous catheters A randomized noninferiority trial comparing

BioMed Research International 15

5-fluorouracil with chlorhexidinesilver sulfadiazine in pre-venting catheter colonizationrdquo Critical Care Medicine vol 38no 11 pp 2095ndash2102 2010

[121] C van Delden T Kohler F Brunner-Ferber B Francois JCarlet and J Pechere ldquoAzithromycin to prevent Pseudomonasaeruginosa ventilator-associated pneumonia by inhibition ofquorum sensing a randomized controlled trialrdquo Intensive CareMedicine vol 38 no 7 pp 1118ndash1125 2012

[122] A R Smyth P M Cifelli C A Ortori et al ldquoGarlic asan inhibitor of Pseudomonas aeruginosa quorum sensing incystic fibrosisndasha pilot randomized controlled trialrdquo PediatricPulmonology vol 45 no 4 pp 356ndash362 2010

Hindawiwwwhindawicom

International Journal of

Volume 2018

Zoology

Hindawiwwwhindawicom Volume 2018

Anatomy Research International

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Hindawiwwwhindawicom Volume 2018

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GenomicsInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

The Scientific World Journal

Volume 2018

Hindawiwwwhindawicom Volume 2018

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawiwwwhindawicom Volume 2018

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Hindawiwwwhindawicom Volume 2018

International Journal of

MicrobiologyHindawiwwwhindawicom

Nucleic AcidsJournal of

Volume 2018

Submit your manuscripts atwwwhindawicom

BioMed Research International 5

Table2Stud

iesd

emon

stratingtheQ

Sdisrup

tionby

signalssynthesis

inhibitio

nAb

breviatio

nsA

Iautoindu

cerenoyl-A

CPeno

yl-acylcarrie

rproteinH

SLL

-hom

oserinelactoneP

HL

prop

ionylh

omoserinelactones

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

In-vitroRa

tsStreptococcus

pneumoniaeD

-39

Sinefung

inInhibitio

nof

AI-2synthesis

via

downregulatinglux

SpfsandspeE

expressio

nInhibitedpn

eumococcalbiofilm

grow

thin

vitro

and

middlee

arcolonizatio

nin

vivo

[62]

In-vitro

Pseudomonas

aerugin

osa

Sinefung

inbutyryl-SAM

and

S-adenosylho

mocysteine

Inhibitin

gacyl-H

SLsig

nals

Inhibitedform

ationof

acovalentacylndashenzyme

[61]

In-vitro

Escherich

iacoli

Methylth

io-D

ADMe-

immucillin-A

Dow

nregulating51015840-m

ethylth

ioadenosine

S-adenosyl-hom

ocysteinen

ucleosidase

hydrolyzes

Disr

uptedkeybacterialpathw

ayso

fmethylatio

npo

lyam

ines

ynthesis

methion

ines

alvageand

quorum

sensing

[64]

Mou

sePlasmodium

falciparum

Triclosan

Inhibitin

genoyl-A

CPredu

ctase

Protectedagainstb

lood

stageso

fmalariaenh

anced

elastic

strength

[66]

6 BioMed Research International

Table3Stud

iesd

emon

stratingQSdisrup

tionby

signalsdegradation

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

In-vitro

Pseudomonas

aerugin

osa

Lacton

aseS

soPo

xDegradatio

nof

thea

cyl-h

omoserinelactones

Inhibitedthev

irulenceo

f51clin

icalPaerugino

saiso

latedfro

mdiabeticfoot

ulcersby

decreasin

gthe

secretionof

proteasesa

ndpyocyanin

andbiofi

lmform

ation

[72]

In-vitrorats

Pseudomonas

aerugin

osaPA

O1

Lacton

aseS

soPo

x-1

Degradatio

nof

thea

cyl-h

omoserinelactones

Decreased

lasB

virulenceg

enea

ctivitypyocyanin

synthesisproteolyticactiv

ityand

biofi

lmform

ation

Redu

cedthem

ortalityof

ratswith

acutep

neum

onia

from

75to

20A

ttenu

ated

lung

damageo

fthe

rat

mod

el

[73]

In-vitro

AbaumanniiS1S

2S3

Engineered

lacton

ase

Degradatio

nof

thea

cyl-h

omoserinelactones

Redu

cedtheb

iomasso

fAbaumanniiassociated

biofi

lms

[74]

In-vitro

Pseudomonas

aerugin

osa

Lacton

aseA

ii810

Degradatio

nof

thea

cyl-h

omoserinelactones

Attenu

ated

VirulenceF

actorsandBiofi

lmFo

rmationDegradedN-butyryl-L-hom

oserine

lacton

eand

N-(3-oxod

odecanoyl)-L-ho

moserine

lacton

eby

723and100

[75]

In-vitro

Pseudomonas

aerugin

osa

Overexpressionof

lacton

asee

nzym

eAHL-1

Degradatio

nof

thea

cyl-h

omoserinelactones

Redu

cedthep

roteasepyocyanin

rham

nolip

ids

Inhibitedthea

ctivities

onthes

warmingmotility

and

biofi

lmform

ation

[76]

In-vitro

Pseudomonas

aerugin

osa

NovelLacton

asec

lonedby

bpiB01bpiB0

4Degradatio

nof

the

N-(3-oxoo

ctanoyl)-L-ho

moserinelactone

Inhibitedmotility

andbiofi

lmform

ation

[77]

In-vitro

Pseudomonas

aerugin

osaPA

O1

Lacton

aseA

iiKDegradatio

nof

thea

cyl-h

omoserinelactones

Inhibitedtheb

iofilm

form

ationandattenu

ates

extracellularp

roteolyticactiv

ityandpyocyanin

prod

uctio

n[78]

In-vitro

Pseudomonas

aerugin

osaPA

O1

N-Acyl-H

omoserine

Lacton

eAcylase

PA2385

Degradatio

nof

3-oxo-C1

2-HSL

and

2-heptyl-3-hydroxy-4(1H)-

quinolon

e

Redu

cedprod

uctio

nof

thev

irulencefactorselastase

andpyocyanin

[85]

In-vitroC

elegans

Pseudomonas

aerugin

osaPA

O1

NADP-depend

ent

short-c

hain

dehydrogenaseredu

ctase

(bpiB0

9)

Inactiv

ationof

N-(3-oxo-do

decano

yl)-L-ho

moserinelactone

(3-oxo-C

12-H

SL)

Redu

cedpyocyaninprod

uctio

ndecreasedmotility

poor

biofi

lmform

ationandabsent

paralysis

ofC

elegans

[91]

In-vitroplant

Pseudomonas

aerugin

osaPA

O1

3-hydroxy-2-methyl-4

(1H)-

quinolon

e

Catalyzingthec

onversionof

PQSto

N-octanoylanthranilica

cidandcarbon

mon

oxide

R edu

cedexpressio

nof

theP

QSbiosyntheticgene

pqsA

expressionof

theP

QS-regu

latedvirulence

determ

inantslectin

Apyocyaninand

rham

nolip

ids

andvirulenceinplant

[94]

BioMed Research International 7

Table4Ap

plications

involvingwith

AHLs

degradationby

anti-QSa

gents3-oxo-C1

2N-3-oxodo

decano

yl-H

SLA

HLN-acyl-h

omoserinelactonesC4

-LHLbu

tenylhom

oserinelactones

C6-LHL

hexano

ylho

moserinelactones

Objectiv

esStrains

Anti-Q

Sagents

Target

Effects

Ref

Tilapia

Aeromonas

hydrophila

AHLlacton

aseA

IO6

Degradatio

nof

thea

cyl-h

omoserinelactones

Maintainedthem

icrovilli

leng

thin

theforegut

oftilapiabut

significantly

lowe

rthanthoseo

fthe

control

[79]

Shrim

pandclam

Vibriona

ceae

strains

Deletionof

AHLs

genesin

34marineV

ibrio

naceae

strains

Acyl-hom

oserinelactonesinactivation

Redu

cedvirulencea

ndmortalityof

them

utant

strains

inbrines

hrim

pandManila

clam

[80]

Shrim

pVibrio

parahaem

olyticu

sAHL-lacton

ase

(AiiA

)Degradatio

nof

thea

cyl-h

omoserinelactones

Inhibitedvibrio

biofi

lmdevelopm

entand

attenu

ated

infectionandmortalityRe

duce

vibrio

viablecoun

tsandbiofi

lmdevelopm

entintheintestin

e[81]

Enzymem

ultilayer

coatings

Chromobacteriu

mviolaceum

CECT

5999Pseud

omonas

aerugin

osaAT

CC

10145

Acylasefrom

Aspergillus

melleus

Degradatio

nof

C6-LHL

Inhibited50violaceinprod

uctio

nby

Chromobacteriu

mviolaceum

CECT

5999R

educes

theP

seud

omonas

aerugin

osaAT

CC10145b

iofilm

form

ationun

derstatic

anddynamiccond

ition

s

[86]

Acylase-containing

polyurethane

coatings

Pseudomonas

aerugin

osaAT

CC

10145a

ndPA

O1

Acylasefrom

Aspergillus

melleus

Degradatio

nof

C4-LHL

C6-LHL

and

3-oxo-C1

2-LH

L

Immob

ilizatio

nof

acylaseled

toan

approxim

ately

60redu

ctionin

biofi

lmform

ation

redu

cethe

secretionof

pyocyanin

[87]

Immob

ilizatio

non

Nanofi

bers

Pseudomonas

aerugin

osaPA

O1

Acylase(EC

35114)

Degradatio

nof

AHLindu

cers

Redu

cedtheb

iofilmbiofoulingform

ationun

der

static

andcontinuo

usflo

wcond

ition

s[88]

8 BioMed Research International

Table5Stud

iesd

emon

stratingQSdisrup

tionby

antib

odiestargetin

g

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

In-vitroandRA

W2647cells

Pseudomonas

aerugin

osa

Antibod

yRS2-1G9

generatedagainsta

3-oxo-do

decano

ylho

moserinelactone

analog

hapten

Targetingtheb

acteria

lN-3-oxo-dod

ecanoyl

homoserinelactone

molecules

Protectm

urineb

onem

arrow-derived

macroph

ages

from

thec

ytotoxiceffectsandalso

preventedthe

activ

ationof

them

itogen-activ

ated

proteinkinase

p38

[100]

In-vitro

Pseudomonas

aerugin

osa

Antibod

yXYD

-11G

2Hydrolyzing

N-3-(oxod

odecanoyl)-L-ho

moserine

lacton

eSupp

ressed

QSsig

nalin

g[101]

In-vitroandmou

semod

elStaphylococcus

aureus

Antibod

yAP4

-24H

11elicitedagainsta

ratio

nally

desig

nedhapten

Sequ

estrationof

thea

utoind

ucingp

eptid

e-4

Supp

ressed

Saureus

pathogenicity

inan

abscess

form

ationmou

semod

elin

vivo

andprovided

completep

rotectionagainsta

lethalStaphylococcus

aureus

challenge

[103]

BioMed Research International 9

Table6Stud

iesd

emon

stratingthes

ynergistice

ffectso

fanti-Q

Sagentsandantib

iotic

s

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

Mice

Pseudomonas

aerugin

osa

Furano

neC-

30ajoeneo

rho

rseradish

juicee

xtractin

Com

binatio

ncurcum

in

QSinhibitio

nenhancethe

sensitivity

ofpathogen

toantib

iotic

sRe

sultedin

anincreasedclearanceo

fPseud

omonas

aerugin

osain

aforeign

-bod

yinfectionmod

el

[107]

In-vitro

Pseudomonas

aerugin

osa

with

tobram

ycin

gentam

icin

and

azith

romycin

Indu

cedconcentrations

ofC1

2-ho

moserine

lacton

eand

C4-h

omoserinelactone

Curcum

inshow

edsynergisticeffectswith

azith

romycin

andgentam

icinC

ombinatio

nuse

redu

cedQS-relatedvirulencefactors

Dow

nregulated

QS-relatedgenes

[112]

In-vitro

Staphylococci

Epigallocatechin-3-gallate

with

Tetracyclin

eInhibitio

nof

thea

ctivity

ofTet(K

)pum

pseffl

uxpu

mps

ofad

ifferentclassTet(B

)En

hanced

theb

acteric

idaleffecto

fTetracyclineo

nStaphylococci

[113]

In-vitro

Pseudomonas

aerugin

osa

N-(2-pyrim

idyl)

butanamideC1

1Dow

nregulationof

rhlrhlA

andlasB

genes

Increasedthes

usceptibilityto

antib

iotic

sand

attenu

ated

thep

atho

genicityof

theb

acteriu

m

[115]

In-vitro

Staphylococcus

aureus

(methicillin-resistant

Sau

reus)

Farnesolwith120573-la

ctam

antib

iotic

s

Inhibitio

nof

lipasea

ctivity

anddisrup

tionof

thec

ytop

lasm

icmem

branethrou

ghthe

leakageo

fpotassiu

mions

Attenu

ated

ther

ateo

fgrowth

ofbacteriaand

coun

terin

gub

iquitous120573-la

ctam

resistancein

bacteria

[116117]

In-vitro

Cele

gansG

aller

iamellonellamice

Burkholderia

cenocepacia

Staphylococcus

aureus

Escherich

iacoli

Baicalin

hydrate

cinn

amaldehyde

hamam

elitann

inwith

Tobram

ycinvancomycin

andclindamycin

Inhibitio

nof

biofi

lmform

ation

QSinhibitio

nenhancethe

sensitivity

ofpathogen

toantib

iotic

s

Com

bining

theu

seof

antib

odyandanti-QSagents

increasedsusceptib

ilityof

theb

acteria

tothe

antib

iotic

and

increasedho

stsurvivalrateaft

erinfection

[118]

10 BioMed Research International

al found in their study [100] that the antibody RS2-1G9can bind to 3-oxo-C12-HSL in the extracellular environmentof Pseudomonas aeruginosa thereby attenuating the inflam-matory response of the host XYD-11G2 antibody has beenshown to catalyze the hydrolysis of 3-oxo-C12-HSL signalingthus inhibiting the pyocyanin production by Gram-negativebacteria [101 102] The monoclonal antibody AP4-24H11 wasfound to block the QS signal of Gram-positive Staphylococcusaureus by interfering with AIP IV [103] Another in vivo studyshowed that the antibody AP4-24H11 could significantlyattenuate the tissue necrosis in the infected model [104]Although these monoclonal antibodies have been identifiedto block the QS signaling of pathogenic bacteria (Table 5)their applications for treating bacterial diseases are still in theinitial stage

45 Combinations of Anti-QS Agents and Antibiotics Com-bining use of antibiotic with an anti-QS agent is the mosteffective clinical strategy for the treatment of bacterial dis-eases at present [105 106] Many studies have confirmed thesynergistic effect of antibiotics and anti-QS agents (Table 6)Ajoene furanone c-30 and horseradish extract have beenrevealed to reduce the expression of virulence factors inPseudomonas aeruginosa and make Pseudomonas aeruginosaeasier to be cleared by tobramycin [107ndash111] Another studyhas confirmed the synergistic effects of curcumin gentam-icin and azithromycin on Pseudomonas aeruginosa that isthe expressions of virulence genes were significantly down-regulated by the combining use of curcumin together withgentamicin or azithromycin and the therapeutic doses ofgentamicin and azithromycin were minimized by curcuminsupplementation [112] The anti-QS compounds such asgallocatechin 3-gallate and caffeic acid enhanced therapeuticeffects on Mycoplasma pneumoniae infection by combininguse with tetracycline ciprofloxacin or gentamicin [113 114]N-(2-pyrimidyl) butylamine was confirmed to enhance theantibacterial effect of tobramycin colistin and ciprofloxacinon Pseudomonas aeruginosa [115] Recent studies [116 117]have shown that both farnesol and hamamelitannin canreduce the virulence of Staphylococcus aureus and increasethe sensitivity of Staphylococcus aureus to 120573-lactam antibi-otics Synergistic effects of hamamelitannin baicalin hydratecinnamaldehyde and antibiotics have been demonstrated indifferent infection models [118 119]These findings imply thatcombining use of antibiotics with ant-QS agents has greattherapeutic potential for bacterial diseases

5 Conclusions

Regulating bacterial QS signaling by QS-targeted agents isan effective strategy to control the production of bacte-rial virulence factors and the formation of biofilm Thisnovel nonantibiotic therapy can inhibit the expression ofpathogenic genes prevent infection and reduce the riskof drug resistance of bacterial cells and has been widelyexploited in recent years A large number of studies haveidentified many anti-QS agents to control the pathogenicphenotypes ofmost bacteria and to attenuate the pathological

damage in various animal infection models However mostanti-QS agents are still in the preclinical phase and morehuman clinical trials are warranted to test their practicalfeasibility The results of several existing clinical studies [120ndash122] on anti-QS agents show that compared with antibioticsthe anti-QS compounds may have potential toxicity andtheir therapeutic effect is not as stable as that of antibioticswhich limited their extensive application Combining use ofanti-QS agents with conventional antibiotics can significantlyimprove the efficacy of therapeutic drugs and decrease thecost of human healthcare and is likely to be the mainapplication method of anti-QS agents for bacterial diseasestreatment in the future

Conflicts of Interest

The authors declare that there are no conflicts of interestregarding the publication of this paper

Acknowledgments

The authors are thankful to the China Scholarship Council(CSC) for both financial support and scholarships Theauthors appreciate Dr Ruiqiang Yang at the Nanjing Agri-culture University for his help on this review This workwas supported by the National Natural Science Foundationof China (31472107) the Youth Science Fund Project of theNational Natural Science Foundation of China (31702126)the Chinese Academy of Sciences lsquoHundred Talentrsquo awardthe National Science Foundation for Distinguished YoungScholars of Hunan Province (2016JJ1015) the Postgradu-ate Research and Innovation Project of Hunan Province(CX2017B348) the Hunan Province ldquoHunan Young Scienceand Technology Innovation Talentrdquo Project (2015RS4053)the Hunan Agricultural University Provincial Outstand-ing Doctoral Dissertation Cultivating Fund (YB2017002)and the Open Foundation of Key Laboratory of Agro-ecological Processes in Subtropical Region Institute ofSubtropical Agriculture Chinese Academy of Sciences(ISA2016101)

References

[1] M Etminan B Carleton J A C Delaney and R PadwalldquoAntibiotics ineffective for prevention of recurrentMIrdquo Journalof Family Practice vol 53 no 7 p 525 2004

[2] F E Akram T El-Tayeb K Abou-Aisha and M El-AzizildquoA combination of silver nanoparticles and visible blue lightenhances the antibacterial efficacy of ineffective antibioticsagainst methicillin-resistant Staphylococcus aureus (MRSA)rdquoAnnals of Clinical Microbiology and Antimicrobials vol 15 no1 p 48 2016

[3] L A Barton and M W Simon ldquoProphylactic antibioticsIneffective or inefficaciousrdquo Clinical Pediatrics vol 53 no 8 p813 2014

[4] J Neumaier ldquoAntibiotics are up to 90 ineffective what reallyhelps in common coldsrdquo MMWmdashFortschritte der Medizin vol153 no 3 pp 18-19 2011

BioMed Research International 11

[5] B Schlemmer ldquoBetter prescribing of antibiotics Preventing therisk of ineffective treatment in current infectionrdquo La Revue dupraticien vol 53 no 14 pp 1525-1526 2003

[6] P Stiefelhagen ldquoSuspected severe pneumonia Antibiotics areineffective - what nowrdquo MMWmdashFortschritte der Medizin vol157 no 17 p 28 2015

[7] Z Li and M Knetsch ldquoAntibacterial strategies for wounddressing preventing infection and stimulating healingrdquoCurrentPharmaceutical Design vol 24 no 8 pp 936ndash951 2018

[8] W Xu S Dong Y Han S Li and Y Liu ldquoHydrogels asantibacterial biomaterialsrdquo Current Pharmaceutical Design vol24 no 8 pp 843ndash854 2018

[9] ldquoMicrobiology by numbersrdquo Nature Reviews Microbiology vol9 no 9 p 628 2011

[10] J P Pearson E C Pesci and B H Iglewski ldquoRoles of Pseu-domonas aeruginosa las and rhl quorum-sensing systems incontrol of elastase and rhamnolipid biosynthesis genesrdquo Journalof Bacteriology vol 179 no 18 pp 5756ndash5767 1997

[11] C Van Delden E C Pesci J P Pearson and B H IglewskildquoStarvation selection restores elastase and rhamnolipid produc-tion in a Pseudomonas aeruginosa quorum-sensing mutantrdquoInfection and Immunity vol 66 no 9 pp 4499ndash4502 1998

[12] L E Dietrich A Price-Whelan A Petersen M Whiteley andD K Newman ldquoThe phenazine pyocyanin is a terminal sig-nalling factor in the quorum sensing network of Pseudomonasaeruginosardquo Molecular Microbiology vol 61 no 5 pp 1308ndash1321 2006

[13] E C Carnes D M Lopez N P Donegan et al ldquoConfinement-induced quorum sensing of individual Staphylococcus aureusbacteriardquoNature Chemical Biology vol 6 no 1 pp 41ndash45 2010

[14] J M Yarwood D J Bartels E M Volper and E P GreenbergldquoQuorum sensing in staphylococcus aureus biofilmsrdquo Journal ofBacteriology vol 186 no 6 pp 1838ndash1850 2004

[15] M J Eickhoff and B L Bassler ldquoSnapShot bacterial quorumsensingrdquo Cell vol 174 no 5 p 1328e1321 2018

[16] M Schuster D Joseph Sexton S P Diggle and E PeterGreenberg ldquoAcyl-homoserine lactone quorum sensing fromevolution to applicationrdquo Annual Review of Microbiology vol67 pp 43ndash63 2013

[17] MH SturmeMKleerebezem J NakayamaA D AkkermansE E Vaugha andWM DeVos ldquoCell to cell communication byautoinducing peptides in gram-positive bacteriardquo Antonie VanLeeuwenhoek vol 81 no 1ndash4 pp 233ndash243 2002

[18] C S Pereira J A Thompson and K B Xavier ldquoAI-2-mediatedsignalling in bacteriardquo FEMS Microbiology Reviews vol 37 no2 pp 156ndash181 2013

[19] M Yang K Sun L Zhou R Yang Z Zhong and J Zhu ldquoFunctional analysis of three AHL autoinducer synthase genes inMesorhizobium loti reveals the important role of quorum sens-ing in symbiotic nodulation rdquoCanadian Journal ofMicrobiologyvol 55 no 2 pp 210ndash214 2009

[20] A Ivanova K Ivanova and T Tzanov ldquoInhibition of Quorum-Sensing A New Paradigm in Controlling Bacterial Virulenceand Biofilm Formationrdquo in Biotechnological Applications ofQuorum Sensing Inhibitors V C Kalia Ed pp 5ndash10 2018

[21] Y Zeng Y Wang Z Yu and Y Huang ldquoHypersensitiveresponse of plasmid-encoded AHL synthase gene to lifestyleand nutrient by Ensifer adhaerens X097rdquo Frontiers in Microbiol-ogy vol 8 p 1160 2017

[22] A O Shpakov ldquoBacterial autoinducing peptidesrdquo Mikrobi-ologiia vol 78 no 3 pp 291ndash303 2009

[23] G J Lyon J S Wright T W Muir and R P Novick ldquoKeydeterminants of receptor activation in the agr autoinducingpeptides of Staphylococcus aureusrdquoBiochemistry vol 41 no 31pp 10095ndash10104 2002

[24] E J Murray and PWilliams ldquoDetection of agr-type autoinduc-ing peptides produced by staphylococcus aureusrdquo Methods inMolecular Biology vol 1673 pp 89ndash96 2018

[25] M J Martin S Clare D Goulding et al ldquoThe agr locus reg-ulates virulence and colonization genes in clostridium difficile027rdquo Journal of Bacteriology vol 195 no 16 pp 3672ndash3681 2013

[26] S Cheraghi L Pourgholi M Shafaati et al ldquoAnalysis ofvirulence genes and accessory gene regulator ( agr ) typesamong methicillin-resistant Staphylococcus aureus strains inIranrdquo Journal of Global Antimicrobial Resistance vol 10 pp 315ndash320 2017

[27] P Gilot G Lina T Cochard and B Poutrel ldquoAnalysis of thegenetic variability of genes encoding the RNA III-activatingcomponents Agr and TRAP in a population of Staphylococcusaureus strains isolated from cows with mastitisrdquo Journal ofClinical Microbiology vol 40 no 11 pp 4060ndash4067 2002

[28] G Lina S Jarraud G Ji et al ldquoTransmembrane topology andhistidine protein kinase activity of AgrC the agr signal receptorin Staphylococcus aureusrdquoMolecular Microbiology vol 28 no3 pp 655ndash662 1998

[29] M Guo S Gamby Y Zheng and H Sintim ldquoSmall moleculeinhibitors of AI-2 signaling in bacteria state-of-the-art andfuture perspectives for anti-quorum sensing agentsrdquo Interna-tional Journal of Molecular Sciences vol 14 no 9 pp 17694ndash17728 2013

[30] JThompson R Oliveira A Djukovic C Ubeda and K XavierldquoManipulation of the quorum sensing signal AI-2 affects theantibiotic-treated gut microbiotardquo Cell Reports vol 10 no 11pp 1861ndash1871 2015

[31] K R Hardie ldquoAutoinducer 2 activity in Escherichia coli culturesupernatants can be actively reduced despite maintenance of anactive synthase LuxSrdquoMicrobiology vol 149 no 3 pp 715ndash7282003

[32] J Wang F Li and Z Tian ldquoRole of microbiota on lunghomeostasis and diseasesrdquo Science China Life Sciences vol 60no 12 pp 1407ndash1415 2017

[33] K Riedel A Gotschlich M Givskov et al ldquoThe cep quorum-sensing system of Burkholderia cepacia H111 controls biofilmformation and swarming motilityrdquoMicrobiology vol 147 no 9pp 2517ndash2528 2001

[34] J C Linnes H Ma and J D Bryers ldquoGiant extracellular matrixbinding protein expression in staphylococcus epidermidis isregulated by biofilm formation and osmotic pressurerdquo CurrentMicrobiology vol 66 no 6 pp 627ndash633 2013

[35] AM Romanı K Fund J Artigas T Schwartz S Sabater andUObst ldquoRelevance of polymeric matrix enzymes during biofilmformationrdquoMicrobial Ecology vol 56 no 3 pp 427ndash436 2008

[36] I Kanwar A K Sah and P K Suresh ldquoBiofilm-mediatedantibiotic-resistant oral bacterial infections mechanism andcombat strategiesrdquo Current Pharmaceutical Design vol 23 no14 pp 2084ndash2095 2017

[37] S Keelara S Thakur and J Patel ldquoBiofilm formation byenvironmental isolates of Salmonella and their sensitivity tonatural antimicrobialsrdquo Foodborne Pathogens and Disease vol13 no 9 pp 509ndash516 2016

[38] F Sepandj H Ceri A Gibb R Read andMOlson ldquoMinimuminhibitory concentration versus minimum biofilm eliminating

12 BioMed Research International

concentration in evaluation of antibiotic sensitivity of entero-cocci causing peritonitisrdquo Peritoneal Dialysis International vol27 no 4 pp 464-465 2007

[39] B A Niemira and E B Solomon ldquoSensitivity of planktonicand biofilm-associated salmonella spp to ionizing radiationrdquoApplied andEnvironmentalMicrobiology vol 71 no 5 pp 2732ndash2736 2005

[40] A M Gamage G Shui M R Wenk and K L Chua ldquoN-Octanoylhomoserine lactone signalling mediated by the BpsI-BpsR quorum sensing system plays a major role in biofilmformationofBurkholderia pseudomalleirdquoMicrobiology vol 157no 4 pp 1176ndash1186 2011

[41] S H Hong M Hegde J Kim X Wang A Jayaraman andT K Wood ldquoSynthetic quorum-sensing circuit to controlconsortial biofilm formation and dispersal in a microfluidicdevicerdquo Nature Communications vol 3 p 613 2012

[42] P Sankar Ganesh and V Ravishankar Rai ldquoAttenuation ofquorum-sensing-dependent virulence factors and biofilm for-mation by medicinal plants against antibiotic resistant Pseu-domonas aeruginosardquo Journal of Traditional and Complemen-tary Medicine vol 8 no 1 pp 170ndash177 2018

[43] P Shih ldquoEffects of quorum-sensing deficiency on Pseudomonasaeruginosa biofilm formation and antibiotic resistancerdquo Journalof Antimicrobial Chemotherapy vol 49 no 2 pp 309ndash314

[44] M I Chernukha I A Shaginian IM Romanova G VMaleevand A L Gintsburg ldquoThe role of ldquoquorum sensingrdquo regula-tion system in symbiotic interaction of bacteria Burkholderiacepacia and Pseudomonas aeruginosa during mixed infectionrdquoZhurnalMikrobiologii Epidemiologii Immunobiologii no 4 pp32ndash37 2006

[45] F M Husain I Ahmad A S Al-Thubiani H H AbulreeshI M AlHazza and F Aqil ldquoLeaf extracts of Mangifera indicaL inhibit quorum sensing - Regulated production of virulencefactors and biofilm in test bacteriardquo Frontiers in Microbiologyvol 8 p 727 2017

[46] D G Renter J G Morris J M Sargeant et al ldquoPreva-lence risk factors O serogroups and virulence profiles ofshiga toxinndashproducing bacteria from cattle production environ-mentsrdquo Journal of Food Protection vol 68 no 8 pp 1556ndash15652005

[47] A R Hauser ldquoPseudomonas aeruginosa So many virulencefactors so little timerdquo Critical Care Medicine vol 39 no 9 pp2193-2194 2011

[48] R Le Berre S Nguyen E Nowak et al ldquoRelative contributionof three main virulence factors in Pseudomonas aeruginosapneumoniardquo Critical Care Medicine vol 39 no 9 pp 2113ndash2120 2011

[49] M M Gallardo-Garcia G Sanchez-Espin R Ivanova-Georgieva et al ldquoRelationship between pathogenic clinicaland virulence factors of Staphylococcus aureus in infectiveendocarditis versus uncomplicated bacteremia a case-controlstudyrdquo European Journal of Clinical Microbiology amp InfectiousDiseases vol 35 no 5 pp 821ndash828 2016

[50] F Sabouni S Mahmoudi A Bahador et al ldquoVirulence factorsof staphylococcus aureus isolates in an iranian referral childrenrsquoshospitalrdquo Osong Public Health and Research Perspectives vol 5no 2 pp 96ndash100 2014

[51] H M Aboushleib H M Omar R Abozahra A Elsheredyand K Baraka ldquoCorrelation of quorum sensing and virulencefactors in Pseudomonas aeruginosa isolates in Egyptrdquo TheJournal of Infection in Developing Countries vol 9 no 10 pp1091ndash1099 2015

[52] R T Sturbelle L F Avila T B Roos et al ldquoThe role ofquorum sensing in Escherichia coli (ETEC) virulence factorsrdquoVeterinary Microbiology vol 180 no 3-4 pp 245ndash252 2015

[53] J E Paczkowski S Mukherjee A R McCready et alldquoFlavonoids suppress Pseudomonas aeruginosa Virulencethrough allosteric inhibition of quorum-sensing receptorsrdquoTheJournal of Biological Chemistry vol 292 no 10 pp 4064ndash40762017

[54] L Weng Y Yang Y Zhang and L Wang ldquoA new syntheticligand that activatesQscRand blocks antibiotic-tolerant biofilmformation in Pseudomonas aeruginosardquo Applied Microbiologyand Biotechnology vol 98 no 6 pp 2565ndash2572 2014

[55] Y-X Yang Z-H Xu Y-Q Zhang J Tian L-X Wengand L-H Wang ldquoA new quorum-sensing inhibitor attenuatesvirulence and decreases antibiotic resistance in Pseudomonasaeruginosardquo Journal of Microbiology vol 50 no 6 pp 987ndash9932012

[56] J N Capilato S V Philippi T Reardon et al ldquoDevelopment ofa novel series of non-natural triaryl agonists and antagonists ofthe Pseudomonas aeruginosa LasR quorum sensing receptorrdquoBioorganic amp Medicinal Chemistry vol 25 no 1 pp 153ndash1652017

[57] C T OrsquoLoughlin L C Miller A Siryaporn K Drescher MF Semmelhack and B L Bassler ldquoA quorum-sensing inhibitorblocks Pseudomonas aeruginosa virulence and biofilm forma-tionrdquo Proceedings of the National Acadamy of Sciences of theUnited States of America vol 110 no 44 pp 17981ndash17986 2013

[58] G D Geske J C OrsquoNeill D M Miller M E Mattmannand H E Blackwell ldquoModulation of bacterial quorum sensingwith synthetic ligands systematic evaluation of N-acylatedhomoserine lactones in multiple species and new insights intotheir mechanisms of actionrdquo Journal of the American ChemicalSociety vol 129 no 44 pp 13613ndash13625 2007

[59] B K Khajanchi M L Kirtley S M Brackman A KChopra and B A McCormick ldquoImmunomodulatory and pro-tective roles of quorum-sensing signaling molecules N-acylhomoserine lactones during infection of mice with aeromonashydrophilardquo Infection and Immunity vol 79 no 7 pp 2646ndash2657 2011

[60] H Tomioka C Sano and Y Tatano ldquoHost-directed therapeu-tics against mycobacterial infectionsrdquo Current PharmaceuticalDesign vol 23 no 18 pp 2644ndash2656 2017

[61] M R Parsek D L Val B L Hanzelka J E Cronan Jr and EP Greenberg ldquoAcyl homoserine-lactone quorum-sensing signalgenerationrdquo Proceedings of the National Acadamy of Sciences ofthe United States of America vol 96 no 8 pp 4360ndash4365 1999

[62] MK Yadav SW Park SW Chae and J J Song ldquoSinefungin anatural nucleoside analogue of S-adenosylmethionine inhibitsStreptococcus pneumoniae biofilm growthrdquo BioMed ResearchInternational vol 2014 Article ID 156987 10 pages 2014

[63] M Hentzer and M Givskov ldquoPharmacological inhibition ofquorum sensing for the treatment of chronic bacterial infec-tionsrdquo The Journal of Clinical Investigation vol 112 no 9 pp1300ndash1307 2003

[64] V Singh G B Evans D H Lenz et al ldquoFemtomolar tran-sition state analogue inhibitors of 5rsquo-methylthioadenosineS-adenosylhomocysteine nucleosidase fromEscherichia colirdquoTheJournal of Biological Chemistry vol 280 no 18 pp 18265ndash182732005

[65] A Priyadarshi E E Kim and K Y Hwang ldquo Structuralinsights into Staphylococcus aureus enoyl-ACP reductase (FabI)

BioMed Research International 13

in complex with NADP and triclosan rdquo Proteins StructureFunction and Bioinformatics vol 78 no 2 pp 480ndash486 2010

[66] N Surolia and A Surolia ldquoTriclosan offers protection againstblood stages of malaria by inhibiting enoyl-ACP reductase ofPlasmodium falciparumrdquoNatureMedicine vol 7 no 2 pp 167ndash173 2001

[67] E Krol and A Becker ldquoRhizobial homologs of the fattyacid transporter FadL facilitate perception of long-chainacyl-homoserine lactone signalsrdquo Proceedings of the NationalAcadamy of Sciences of the United States of America vol 111 no29 pp 10702ndash10707 2014

[68] J L Copitch R N Whitehead and M A Webber ldquoPrevalenceof decreased susceptibility to triclosan in Salmonella entericaisolates fromanimals andhumans andassociationwithmultipledrug resistancerdquo International Journal of Antimicrobial Agentsvol 36 no 3 pp 247ndash251 2010

[69] S Lu N Wang S Ma X Hu L Kang and Y Yu ldquoParabensand triclosan in shellfish fromShenzhen coastal waters bioindi-cation of pollution and human health risksrdquo EnvironmentalPollution vol 246 pp 257ndash263 2018

[70] N Huma P Shankar J Kushwah et al ldquoDiversity and poly-morphism in AHL-Lactonase gene (aiiA) of Bacillusrdquo Journalof Microbiology and Biotechnology vol 21 no 10 pp 1001ndash10112011

[71] S Y Park B J Hwang M Shin J Kim H Kim and J LeeldquoN-acylhomoserine lactonase-producingRhodococcussppwithdifferent AHL-degrading activitiesrdquo FEMSMicrobiology Lettersvol 261 no 1 pp 102ndash108 2006

[72] A Guendouze L Plener J Bzdrenga et al ldquoEffect of quo-rum quenching lactonase in clinical isolates of pseudomonasaeruginosa and comparison with quorum sensing inhibitorsrdquoFrontiers in Microbiology vol 8 p 227 2017

[73] S Hraiech J Hiblot J Lafleur et al ldquoInhaled lactonase reducespseudomonas aeruginosa quorum sensing and mortality in ratpneumoniardquo PLoS ONE vol 9 no 10 Article ID e107125 2014

[74] J Y Chow Y Yang S B Tay K L Chua and W S YewldquoDisruption of biofilm formation by the human pathogenacinetobacter baumannii using engineered quorum-quenchinglactonasesrdquoAntimicrobial Agents andChemotherapy vol 58 no3 pp 1802ndash1805 2014

[75] X FanM Liang L Wang R Chen H Li and X Liu ldquoAii810 anovel cold-adapted N-acylhomoserine lactonase discovered inametagenome can strongly attenuate Pseudomonas aeruginosavirulence factors and biofilm formationrdquo Frontiers in Microbiol-ogy vol 8 p 1950 2017

[76] MM Sakr KM AboshanabW F ElkhatibMA Yassien andN AHassouna ldquoOverexpressed recombinant quorumquench-ing lactonase reduces the virulence motility and biofilm for-mationofmultidrug-resistant Pseudomonas aeruginosa clinicalisolatesrdquo Appl Microbiol Biotechnol vol 102 no 24 pp 10613ndash10622 2018

[77] C Schipper C Hornung P Bijtenhoorn M Quitschau SGrond andW R Streit ldquoMetagenome-derived clones encodingtwo novel lactonase family proteins involved in biofilm inhibi-tion in pseudomonas aeruginosardquo Applied and EnvironmentalMicrobiology vol 75 no 1 pp 224ndash233 2008

[78] W Dong J Zhu X Guo et al ldquoCharacterization of AiiKan AHL lactonase from Kurthia huakui LAM0618T and itsapplication in quorum quenching on Pseudomonas aeruginosaPAO1rdquo Scientific Reports vol 8 no 1 p 6013 2018

[79] W Liu C Ran Z Liu et al ldquoEffects of dietary Lactobacillusplantarum and AHL lactonase on the control of Aeromonas

hydrophila infection in tilapiardquoMicrobiologyopen vol 5 no 4pp 687ndash699 2016

[80] M Torres J C Reina J C Fuentes-Monteverde et al ldquoAHL-lactonase expression in three marine emerging pathogenicVibrio spp reduces virulence and mortality in brine shrimp(Artemia salina) and Manila clam (Venerupis philippinarum)rdquoPLoS ONE vol 13 no 4 Article ID e0195176 2018

[81] G Vinoj B Vaseeharan S Thomas A J Spiers and S ShanthildquoQuorum-quenching activity of the AHL-lactonase from bacil-lus licheniformis DAHB1 inhibits vibrio biofilm formation invitro and reduces shrimp intestinal colonisation andmortalityrdquoMarine Biotechnology vol 16 no 6 pp 707ndash715 2014

[82] V C Kalia ldquoIn search of versatile organisms for quorum-sensing inhibitors acyl homoserine lactones (AHL)-acylaseand AHL-lactonaserdquo FEMS Microbiology Letters vol 359 no2 p 143 2014

[83] V B Maisuria and A S Nerurkar ldquoInterference of quorumsensing by Delftia sp VM4 depends on the activity of a noveln-acylhomoserine lactone-acylaserdquo PLoS ONE vol 10 no 9Article ID e0138034 2015

[84] R Mukherji N K Varshney P Panigrahi C Suresh and APrabhune ldquoA new role for penicillin acylases degradation ofacyl homoserine lactone quorum sensing signals by Kluyveracitrophila penicillin G acylaserdquo Enzyme and Microbial Technol-ogy vol 56 pp 1ndash7 2014

[85] C F Sio L G Otten R H Cool et al ldquoQuorum quenchingby an N-acyl-homoserine lactone acylase from Pseudomonasaeruginosa PAO1rdquo Infection and Immunity vol 74 no 3 pp1673ndash1682 2006

[86] K Ivanova M M Fernandes E Mendoza and T TzanovldquoEnzyme multilayer coatings inhibit Pseudomonas aeruginosabiofilm formation on urinary cathetersrdquo Applied Microbiologyand Biotechnology vol 99 no 10 pp 4373ndash4385 2015

[87] N Grover J G Plaks S R Summers G R Chado M J Schurrand J L Kaar ldquoAcylase-containing polyurethane coatings withanti-biofilm activityrdquo Biotechnology and Bioengineering vol 113no 12 pp 2535ndash2543 2016

[88] J Lee I Lee J Nam D S Hwang K-M Yeon and JKim ldquoImmobilization and stabilization of acylase on carboxy-lated polyaniline nanofibers for highly effective antifoulingapplication via quorum quenchingrdquo ACS Applied Materials ampInterfaces vol 9 no 18 pp 15424ndash15432 2017

[89] S Uroz S R Chhabra M Camara P Williams P Ogerand Y Dessaux ldquoN-acylhomoserine lactone quorum-sensingmolecules are modified and degraded by Rhodococcus ery-thropolis W2 by both amidolytic and novel oxidoreductaseactivitiesrdquoMicrobiology vol 151 no 10 pp 3313ndash3322 2005

[90] B Eva and S Maria ldquoMicrobial secondary metabolites asinhibitors of pharmaceutically important transferases and oxi-doreductasesrdquo Ceska Slov Farm vol 61 no 3 pp 107ndash114 2012

[91] P Bijtenhoorn H Mayerhofer J Muller-Dieckmann et alldquoA novel metagenomic Short-Chain dehydrogenasereductaseattenuates pseudomonas Aeruginosa biofilm formation andvirulence on Caenorhabditis elegansrdquo PLoS ONE vol 6 no 10Article ID e26278 2011

[92] J D Wildschut R M Lang J K Voordouw and G Voor-douw ldquoRubredoxin oxygen oxidoreductase enhances survivalof desulfovibrio vulgaris hildenborough under microaerophilicconditionsrdquo Journal of Bacteriology vol 188 no 17 pp 6253ndash6260 2006

14 BioMed Research International

[93] X Zhang S Ou-yang JWang L Liao RWu and JWei ldquoCon-struction of antibacterial surface via layer-by-layer methodrdquoCurrent Pharmaceutical Design vol 24 no 8 pp 926ndash935 2018

[94] C Pustelny A Albers K Buldt-Karentzopoulos et al ldquoDiox-ygenase-mediated quenching of quinolone-dependent quorumsensing in pseudomonas aeruginosardquoChemistry amp Biology vol16 no 12 pp 1259ndash1267 2009

[95] J T Hodgkinson W R Galloway M Welch and DR Spring ldquoMicrowave-assisted preparation of the quorum-sensing molecule 2-heptyl-3-hydroxy-4(1H)-quinolone andstructurally related analogsrdquo Nature Protocols vol 7 no 6 pp1184ndash1192 2012

[96] F Witzgall T Depke M Hoffmann et al ldquoThe alkylquinolonerepertoire of Pseudomonas aeruginosa is linked to structuralflexibility of the fabh-like 2-heptyl-3-hydroxy-4(1H)-quinolone(PQS) biosynthesis enzyme PqsBCrdquo ChemBioChem vol 19 no14 pp 1531ndash1544 2018

[97] L Andresen E Sala V Koiv and A Mae ldquoA role for theRcs phosphorelay in regulating expression of plant cell walldegrading enzymes in Pectobacterium carotovorum subspcarotovorumrdquoMicrobiology vol 156 no 5 pp 1323ndash1334 2010

[98] L Andresen V Koiv T Alamae and A Mae ldquoThe Rcs phos-phorelay modulates the expression of plant cell wall degradingenzymes and virulence in Pectobacterium carotovorum sspcarotovorumrdquo FEMS Microbiology Letters vol 273 no 2 pp229ndash238 2007

[99] R K Gupta S Chhibber and K Harjai ldquoAcyl homoserinelactones from culture supernatants of pseudomonas aeruginosaaccelerate host immunomodulationrdquo PLoS ONE vol 6 no 6Article ID e20860 2011

[100] G F Kaufmann J Park J M Mee R J Ulevitch and KD Janda ldquoThe quorum quenching antibody RS2-1G9 protectsmacrophages from the cytotoxic effects of the Pseudomonasaeruginosa quorum sensing signalling molecule N-3-oxo-dodecanoyl-homoserine lactonerdquo Molecular Immunology vol45 no 9 pp 2710ndash2714 2008

[101] S Koul J Prakash A Mishra and V C Kalia ldquoPotential emer-gence of multi-quorum sensing inhibitor resistant (MQSIR)bacteriardquo Indian Journal of Microbiology vol 56 no 1 pp 1ndash182016

[102] T Praneenararat A G Palmer and H E Blackwell ldquoChemicalmethods to interrogate bacterial quorum sensing pathwaysrdquoOrganicampBiomolecular Chemistry vol 10 no 41 pp 8189ndash81992012

[103] J Park R Jagasia G F Kaufmann et al ldquoInfection controlby antibody disruption of bacterial quorum sensing signalingrdquoChemistry amp Biology vol 14 no 10 pp 1119ndash1127 2007

[104] C Grandclement M Tannieres S Morera Y Dessaux DFaure andM Camara ldquoQuorum quenching role in nature andapplied developmentsrdquo FEMSMicrobiology Reviews vol 40 no1 pp 86ndash116 2016

[105] MHan J GuG F Gao andW J Liu ldquoChina in action nationalstrategies to combat against emerging infectious diseasesrdquoScience China Life Sciences vol 60 no 12 pp 1383ndash1385 2017

[106] J Liu H Yu Y Huang et al ldquoComplete genome sequence ofa novel bacteriophage infecting Bradyrhizobium diazoefficiensUSDA110rdquo Science China Life Sciences vol 61 no 1 pp 118ndash1212018

[107] L D Christensen M van Gennip T H Jakobsen et alldquoSynergistic antibacterial efficacy of early combination treat-ment with tobramycin and quorum-sensing inhibitors against

Pseudomonas aeruginosa in an intraperitoneal foreign-bodyinfection mouse modelrdquo Journal of Antimicrobial Chemother-apy vol 67 no 5 pp 1198ndash1206 2012

[108] J Fong M Yuan T H Jakobsen et al ldquoDisulfide bond-containing ajoene analogues as novel quorum sensinginhibitors of Pseudomonas aeruginosardquo Journal of MedicinalChemistry vol 60 no 1 pp 215ndash227 2017

[109] R Garcıa-Contreras M Martınez-Vazquez N VelazquezGuadarrama et al ldquo Resistance to the quorum-quenchingcompounds brominated furanone C-30 and 5-fluorouracil inPseudomonas aeruginosa clinical isolates rdquo Pathogens and Dis-ease vol 68 no 1 pp 8ndash11 2013

[110] T H Jakobsen S K Bragason R K Phipps et al ldquoFood as asource for quorum sensing inhibitors iberin from horseradishrevealed as a quorum sensing inhibitor of pseudomonas aerug-inosardquo Applied and Environmental Microbiology vol 78 no 7pp 2410ndash2421 2012

[111] A Vadekeetil H Saini S Chhibber and K Harjai ldquo Exploitingthe antivirulence efficacy of an ajoene-ciprofloxacin combina-tion against Pseudomonas aeruginosa biofilm associatedmurineacute pyelonephritis rdquo Biofouling vol 32 no 4 pp 371ndash3822016

[112] S Bahari H Zeighami H Mirshahabi S Roudashti and FHaghi ldquoInhibition of pseudomonas aeruginosa quorum sensingby subinhibitory concentrations of curcumin with gentamicinand azithromycinrdquo Journal of Global Antimicrobial Resistancevol 10 pp 21ndash28 2017

[113] A S Roccaro A R Blanco F Giuliano D Rusciano and VEnea ldquoEpigallocatechin-gallate enhances the activity of tetra-cycline in staphylococci by inhibiting its efflux from bacterialcellsrdquo Antimicrobial Agents and Chemotherapy vol 48 no 6pp 1968ndash1973 2004

[114] C Chu J Deng Y Man and Y Qu ldquoGreen tea extractsepigallocatechin-3-gallate for different treatmentsrdquo BioMedResearch International vol 2017 Article ID 5615647 9 pages2017

[115] A Furiga B Lajoie S El Hage G Baziard and C RoquesldquoImpairment of pseudomonas aeruginosa biofilm resistance toantibiotics by combining the drugs with a new quorum-sensinginhibitorrdquo Antimicrobial Agents and Chemotherapy vol 60 no3 pp 1676ndash1686 2016

[116] Y Inoue N Togashi and H Hamashima ldquoFarnesol-induceddisruption of the staphylococcus aureus cytoplasmic mem-branerdquo Biological and Pharmaceutical Bulletin vol 39 no 5 pp653ndash656 2016

[117] C Kim D Hesek M Lee and S Mobashery ldquoPotentiationof the activity of beta-lactam antibiotics by farnesol and itsderivativesrdquo Bioorganic amp Medicinal Chemistry Letters vol 28no 4 pp 642ndash645 2018

[118] G Brackman P Cos L Maes H J Nelis and T Coenye ldquoQuo-rum sensing inhibitors increase the susceptibility of bacterialbiofilms to antibiotics in vitro and in vivordquoAntimicrobial Agentsand Chemotherapy vol 55 no 6 pp 2655ndash2661 2011

[119] G Brackman K Breyne R De Rycke et al ldquoThe quorum sens-ing inhibitor hamamelitannin increases antibiotic susceptibilityof staphylococcus aureus biofilms by affecting peptidoglycanbiosynthesis and eDNA releaserdquo Scientific Reports vol 6 ArticleID 20321 2016

[120] J M Walz R L Avelar K J Longtine K L Carter L A Mer-mel and S O Heard ldquoAnti-infective external coating of centralvenous catheters A randomized noninferiority trial comparing

BioMed Research International 15

5-fluorouracil with chlorhexidinesilver sulfadiazine in pre-venting catheter colonizationrdquo Critical Care Medicine vol 38no 11 pp 2095ndash2102 2010

[121] C van Delden T Kohler F Brunner-Ferber B Francois JCarlet and J Pechere ldquoAzithromycin to prevent Pseudomonasaeruginosa ventilator-associated pneumonia by inhibition ofquorum sensing a randomized controlled trialrdquo Intensive CareMedicine vol 38 no 7 pp 1118ndash1125 2012

[122] A R Smyth P M Cifelli C A Ortori et al ldquoGarlic asan inhibitor of Pseudomonas aeruginosa quorum sensing incystic fibrosisndasha pilot randomized controlled trialrdquo PediatricPulmonology vol 45 no 4 pp 356ndash362 2010

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Nucleic AcidsJournal of

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Submit your manuscripts atwwwhindawicom

6 BioMed Research International

Table3Stud

iesd

emon

stratingQSdisrup

tionby

signalsdegradation

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

In-vitro

Pseudomonas

aerugin

osa

Lacton

aseS

soPo

xDegradatio

nof

thea

cyl-h

omoserinelactones

Inhibitedthev

irulenceo

f51clin

icalPaerugino

saiso

latedfro

mdiabeticfoot

ulcersby

decreasin

gthe

secretionof

proteasesa

ndpyocyanin

andbiofi

lmform

ation

[72]

In-vitrorats

Pseudomonas

aerugin

osaPA

O1

Lacton

aseS

soPo

x-1

Degradatio

nof

thea

cyl-h

omoserinelactones

Decreased

lasB

virulenceg

enea

ctivitypyocyanin

synthesisproteolyticactiv

ityand

biofi

lmform

ation

Redu

cedthem

ortalityof

ratswith

acutep

neum

onia

from

75to

20A

ttenu

ated

lung

damageo

fthe

rat

mod

el

[73]

In-vitro

AbaumanniiS1S

2S3

Engineered

lacton

ase

Degradatio

nof

thea

cyl-h

omoserinelactones

Redu

cedtheb

iomasso

fAbaumanniiassociated

biofi

lms

[74]

In-vitro

Pseudomonas

aerugin

osa

Lacton

aseA

ii810

Degradatio

nof

thea

cyl-h

omoserinelactones

Attenu

ated

VirulenceF

actorsandBiofi

lmFo

rmationDegradedN-butyryl-L-hom

oserine

lacton

eand

N-(3-oxod

odecanoyl)-L-ho

moserine

lacton

eby

723and100

[75]

In-vitro

Pseudomonas

aerugin

osa

Overexpressionof

lacton

asee

nzym

eAHL-1

Degradatio

nof

thea

cyl-h

omoserinelactones

Redu

cedthep

roteasepyocyanin

rham

nolip

ids

Inhibitedthea

ctivities

onthes

warmingmotility

and

biofi

lmform

ation

[76]

In-vitro

Pseudomonas

aerugin

osa

NovelLacton

asec

lonedby

bpiB01bpiB0

4Degradatio

nof

the

N-(3-oxoo

ctanoyl)-L-ho

moserinelactone

Inhibitedmotility

andbiofi

lmform

ation

[77]

In-vitro

Pseudomonas

aerugin

osaPA

O1

Lacton

aseA

iiKDegradatio

nof

thea

cyl-h

omoserinelactones

Inhibitedtheb

iofilm

form

ationandattenu

ates

extracellularp

roteolyticactiv

ityandpyocyanin

prod

uctio

n[78]

In-vitro

Pseudomonas

aerugin

osaPA

O1

N-Acyl-H

omoserine

Lacton

eAcylase

PA2385

Degradatio

nof

3-oxo-C1

2-HSL

and

2-heptyl-3-hydroxy-4(1H)-

quinolon

e

Redu

cedprod

uctio

nof

thev

irulencefactorselastase

andpyocyanin

[85]

In-vitroC

elegans

Pseudomonas

aerugin

osaPA

O1

NADP-depend

ent

short-c

hain

dehydrogenaseredu

ctase

(bpiB0

9)

Inactiv

ationof

N-(3-oxo-do

decano

yl)-L-ho

moserinelactone

(3-oxo-C

12-H

SL)

Redu

cedpyocyaninprod

uctio

ndecreasedmotility

poor

biofi

lmform

ationandabsent

paralysis

ofC

elegans

[91]

In-vitroplant

Pseudomonas

aerugin

osaPA

O1

3-hydroxy-2-methyl-4

(1H)-

quinolon

e

Catalyzingthec

onversionof

PQSto

N-octanoylanthranilica

cidandcarbon

mon

oxide

R edu

cedexpressio

nof

theP

QSbiosyntheticgene

pqsA

expressionof

theP

QS-regu

latedvirulence

determ

inantslectin

Apyocyaninand

rham

nolip

ids

andvirulenceinplant

[94]

BioMed Research International 7

Table4Ap

plications

involvingwith

AHLs

degradationby

anti-QSa

gents3-oxo-C1

2N-3-oxodo

decano

yl-H

SLA

HLN-acyl-h

omoserinelactonesC4

-LHLbu

tenylhom

oserinelactones

C6-LHL

hexano

ylho

moserinelactones

Objectiv

esStrains

Anti-Q

Sagents

Target

Effects

Ref

Tilapia

Aeromonas

hydrophila

AHLlacton

aseA

IO6

Degradatio

nof

thea

cyl-h

omoserinelactones

Maintainedthem

icrovilli

leng

thin

theforegut

oftilapiabut

significantly

lowe

rthanthoseo

fthe

control

[79]

Shrim

pandclam

Vibriona

ceae

strains

Deletionof

AHLs

genesin

34marineV

ibrio

naceae

strains

Acyl-hom

oserinelactonesinactivation

Redu

cedvirulencea

ndmortalityof

them

utant

strains

inbrines

hrim

pandManila

clam

[80]

Shrim

pVibrio

parahaem

olyticu

sAHL-lacton

ase

(AiiA

)Degradatio

nof

thea

cyl-h

omoserinelactones

Inhibitedvibrio

biofi

lmdevelopm

entand

attenu

ated

infectionandmortalityRe

duce

vibrio

viablecoun

tsandbiofi

lmdevelopm

entintheintestin

e[81]

Enzymem

ultilayer

coatings

Chromobacteriu

mviolaceum

CECT

5999Pseud

omonas

aerugin

osaAT

CC

10145

Acylasefrom

Aspergillus

melleus

Degradatio

nof

C6-LHL

Inhibited50violaceinprod

uctio

nby

Chromobacteriu

mviolaceum

CECT

5999R

educes

theP

seud

omonas

aerugin

osaAT

CC10145b

iofilm

form

ationun

derstatic

anddynamiccond

ition

s

[86]

Acylase-containing

polyurethane

coatings

Pseudomonas

aerugin

osaAT

CC

10145a

ndPA

O1

Acylasefrom

Aspergillus

melleus

Degradatio

nof

C4-LHL

C6-LHL

and

3-oxo-C1

2-LH

L

Immob

ilizatio

nof

acylaseled

toan

approxim

ately

60redu

ctionin

biofi

lmform

ation

redu

cethe

secretionof

pyocyanin

[87]

Immob

ilizatio

non

Nanofi

bers

Pseudomonas

aerugin

osaPA

O1

Acylase(EC

35114)

Degradatio

nof

AHLindu

cers

Redu

cedtheb

iofilmbiofoulingform

ationun

der

static

andcontinuo

usflo

wcond

ition

s[88]

8 BioMed Research International

Table5Stud

iesd

emon

stratingQSdisrup

tionby

antib

odiestargetin

g

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

In-vitroandRA

W2647cells

Pseudomonas

aerugin

osa

Antibod

yRS2-1G9

generatedagainsta

3-oxo-do

decano

ylho

moserinelactone

analog

hapten

Targetingtheb

acteria

lN-3-oxo-dod

ecanoyl

homoserinelactone

molecules

Protectm

urineb

onem

arrow-derived

macroph

ages

from

thec

ytotoxiceffectsandalso

preventedthe

activ

ationof

them

itogen-activ

ated

proteinkinase

p38

[100]

In-vitro

Pseudomonas

aerugin

osa

Antibod

yXYD

-11G

2Hydrolyzing

N-3-(oxod

odecanoyl)-L-ho

moserine

lacton

eSupp

ressed

QSsig

nalin

g[101]

In-vitroandmou

semod

elStaphylococcus

aureus

Antibod

yAP4

-24H

11elicitedagainsta

ratio

nally

desig

nedhapten

Sequ

estrationof

thea

utoind

ucingp

eptid

e-4

Supp

ressed

Saureus

pathogenicity

inan

abscess

form

ationmou

semod

elin

vivo

andprovided

completep

rotectionagainsta

lethalStaphylococcus

aureus

challenge

[103]

BioMed Research International 9

Table6Stud

iesd

emon

stratingthes

ynergistice

ffectso

fanti-Q

Sagentsandantib

iotic

s

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

Mice

Pseudomonas

aerugin

osa

Furano

neC-

30ajoeneo

rho

rseradish

juicee

xtractin

Com

binatio

ncurcum

in

QSinhibitio

nenhancethe

sensitivity

ofpathogen

toantib

iotic

sRe

sultedin

anincreasedclearanceo

fPseud

omonas

aerugin

osain

aforeign

-bod

yinfectionmod

el

[107]

In-vitro

Pseudomonas

aerugin

osa

with

tobram

ycin

gentam

icin

and

azith

romycin

Indu

cedconcentrations

ofC1

2-ho

moserine

lacton

eand

C4-h

omoserinelactone

Curcum

inshow

edsynergisticeffectswith

azith

romycin

andgentam

icinC

ombinatio

nuse

redu

cedQS-relatedvirulencefactors

Dow

nregulated

QS-relatedgenes

[112]

In-vitro

Staphylococci

Epigallocatechin-3-gallate

with

Tetracyclin

eInhibitio

nof

thea

ctivity

ofTet(K

)pum

pseffl

uxpu

mps

ofad

ifferentclassTet(B

)En

hanced

theb

acteric

idaleffecto

fTetracyclineo

nStaphylococci

[113]

In-vitro

Pseudomonas

aerugin

osa

N-(2-pyrim

idyl)

butanamideC1

1Dow

nregulationof

rhlrhlA

andlasB

genes

Increasedthes

usceptibilityto

antib

iotic

sand

attenu

ated

thep

atho

genicityof

theb

acteriu

m

[115]

In-vitro

Staphylococcus

aureus

(methicillin-resistant

Sau

reus)

Farnesolwith120573-la

ctam

antib

iotic

s

Inhibitio

nof

lipasea

ctivity

anddisrup

tionof

thec

ytop

lasm

icmem

branethrou

ghthe

leakageo

fpotassiu

mions

Attenu

ated

ther

ateo

fgrowth

ofbacteriaand

coun

terin

gub

iquitous120573-la

ctam

resistancein

bacteria

[116117]

In-vitro

Cele

gansG

aller

iamellonellamice

Burkholderia

cenocepacia

Staphylococcus

aureus

Escherich

iacoli

Baicalin

hydrate

cinn

amaldehyde

hamam

elitann

inwith

Tobram

ycinvancomycin

andclindamycin

Inhibitio

nof

biofi

lmform

ation

QSinhibitio

nenhancethe

sensitivity

ofpathogen

toantib

iotic

s

Com

bining

theu

seof

antib

odyandanti-QSagents

increasedsusceptib

ilityof

theb

acteria

tothe

antib

iotic

and

increasedho

stsurvivalrateaft

erinfection

[118]

10 BioMed Research International

al found in their study [100] that the antibody RS2-1G9can bind to 3-oxo-C12-HSL in the extracellular environmentof Pseudomonas aeruginosa thereby attenuating the inflam-matory response of the host XYD-11G2 antibody has beenshown to catalyze the hydrolysis of 3-oxo-C12-HSL signalingthus inhibiting the pyocyanin production by Gram-negativebacteria [101 102] The monoclonal antibody AP4-24H11 wasfound to block the QS signal of Gram-positive Staphylococcusaureus by interfering with AIP IV [103] Another in vivo studyshowed that the antibody AP4-24H11 could significantlyattenuate the tissue necrosis in the infected model [104]Although these monoclonal antibodies have been identifiedto block the QS signaling of pathogenic bacteria (Table 5)their applications for treating bacterial diseases are still in theinitial stage

45 Combinations of Anti-QS Agents and Antibiotics Com-bining use of antibiotic with an anti-QS agent is the mosteffective clinical strategy for the treatment of bacterial dis-eases at present [105 106] Many studies have confirmed thesynergistic effect of antibiotics and anti-QS agents (Table 6)Ajoene furanone c-30 and horseradish extract have beenrevealed to reduce the expression of virulence factors inPseudomonas aeruginosa and make Pseudomonas aeruginosaeasier to be cleared by tobramycin [107ndash111] Another studyhas confirmed the synergistic effects of curcumin gentam-icin and azithromycin on Pseudomonas aeruginosa that isthe expressions of virulence genes were significantly down-regulated by the combining use of curcumin together withgentamicin or azithromycin and the therapeutic doses ofgentamicin and azithromycin were minimized by curcuminsupplementation [112] The anti-QS compounds such asgallocatechin 3-gallate and caffeic acid enhanced therapeuticeffects on Mycoplasma pneumoniae infection by combininguse with tetracycline ciprofloxacin or gentamicin [113 114]N-(2-pyrimidyl) butylamine was confirmed to enhance theantibacterial effect of tobramycin colistin and ciprofloxacinon Pseudomonas aeruginosa [115] Recent studies [116 117]have shown that both farnesol and hamamelitannin canreduce the virulence of Staphylococcus aureus and increasethe sensitivity of Staphylococcus aureus to 120573-lactam antibi-otics Synergistic effects of hamamelitannin baicalin hydratecinnamaldehyde and antibiotics have been demonstrated indifferent infection models [118 119]These findings imply thatcombining use of antibiotics with ant-QS agents has greattherapeutic potential for bacterial diseases

5 Conclusions

Regulating bacterial QS signaling by QS-targeted agents isan effective strategy to control the production of bacte-rial virulence factors and the formation of biofilm Thisnovel nonantibiotic therapy can inhibit the expression ofpathogenic genes prevent infection and reduce the riskof drug resistance of bacterial cells and has been widelyexploited in recent years A large number of studies haveidentified many anti-QS agents to control the pathogenicphenotypes ofmost bacteria and to attenuate the pathological

damage in various animal infection models However mostanti-QS agents are still in the preclinical phase and morehuman clinical trials are warranted to test their practicalfeasibility The results of several existing clinical studies [120ndash122] on anti-QS agents show that compared with antibioticsthe anti-QS compounds may have potential toxicity andtheir therapeutic effect is not as stable as that of antibioticswhich limited their extensive application Combining use ofanti-QS agents with conventional antibiotics can significantlyimprove the efficacy of therapeutic drugs and decrease thecost of human healthcare and is likely to be the mainapplication method of anti-QS agents for bacterial diseasestreatment in the future

Conflicts of Interest

The authors declare that there are no conflicts of interestregarding the publication of this paper

Acknowledgments

The authors are thankful to the China Scholarship Council(CSC) for both financial support and scholarships Theauthors appreciate Dr Ruiqiang Yang at the Nanjing Agri-culture University for his help on this review This workwas supported by the National Natural Science Foundationof China (31472107) the Youth Science Fund Project of theNational Natural Science Foundation of China (31702126)the Chinese Academy of Sciences lsquoHundred Talentrsquo awardthe National Science Foundation for Distinguished YoungScholars of Hunan Province (2016JJ1015) the Postgradu-ate Research and Innovation Project of Hunan Province(CX2017B348) the Hunan Province ldquoHunan Young Scienceand Technology Innovation Talentrdquo Project (2015RS4053)the Hunan Agricultural University Provincial Outstand-ing Doctoral Dissertation Cultivating Fund (YB2017002)and the Open Foundation of Key Laboratory of Agro-ecological Processes in Subtropical Region Institute ofSubtropical Agriculture Chinese Academy of Sciences(ISA2016101)

References

[1] M Etminan B Carleton J A C Delaney and R PadwalldquoAntibiotics ineffective for prevention of recurrentMIrdquo Journalof Family Practice vol 53 no 7 p 525 2004

[2] F E Akram T El-Tayeb K Abou-Aisha and M El-AzizildquoA combination of silver nanoparticles and visible blue lightenhances the antibacterial efficacy of ineffective antibioticsagainst methicillin-resistant Staphylococcus aureus (MRSA)rdquoAnnals of Clinical Microbiology and Antimicrobials vol 15 no1 p 48 2016

[3] L A Barton and M W Simon ldquoProphylactic antibioticsIneffective or inefficaciousrdquo Clinical Pediatrics vol 53 no 8 p813 2014

[4] J Neumaier ldquoAntibiotics are up to 90 ineffective what reallyhelps in common coldsrdquo MMWmdashFortschritte der Medizin vol153 no 3 pp 18-19 2011

BioMed Research International 11

[5] B Schlemmer ldquoBetter prescribing of antibiotics Preventing therisk of ineffective treatment in current infectionrdquo La Revue dupraticien vol 53 no 14 pp 1525-1526 2003

[6] P Stiefelhagen ldquoSuspected severe pneumonia Antibiotics areineffective - what nowrdquo MMWmdashFortschritte der Medizin vol157 no 17 p 28 2015

[7] Z Li and M Knetsch ldquoAntibacterial strategies for wounddressing preventing infection and stimulating healingrdquoCurrentPharmaceutical Design vol 24 no 8 pp 936ndash951 2018

[8] W Xu S Dong Y Han S Li and Y Liu ldquoHydrogels asantibacterial biomaterialsrdquo Current Pharmaceutical Design vol24 no 8 pp 843ndash854 2018

[9] ldquoMicrobiology by numbersrdquo Nature Reviews Microbiology vol9 no 9 p 628 2011

[10] J P Pearson E C Pesci and B H Iglewski ldquoRoles of Pseu-domonas aeruginosa las and rhl quorum-sensing systems incontrol of elastase and rhamnolipid biosynthesis genesrdquo Journalof Bacteriology vol 179 no 18 pp 5756ndash5767 1997

[11] C Van Delden E C Pesci J P Pearson and B H IglewskildquoStarvation selection restores elastase and rhamnolipid produc-tion in a Pseudomonas aeruginosa quorum-sensing mutantrdquoInfection and Immunity vol 66 no 9 pp 4499ndash4502 1998

[12] L E Dietrich A Price-Whelan A Petersen M Whiteley andD K Newman ldquoThe phenazine pyocyanin is a terminal sig-nalling factor in the quorum sensing network of Pseudomonasaeruginosardquo Molecular Microbiology vol 61 no 5 pp 1308ndash1321 2006

[13] E C Carnes D M Lopez N P Donegan et al ldquoConfinement-induced quorum sensing of individual Staphylococcus aureusbacteriardquoNature Chemical Biology vol 6 no 1 pp 41ndash45 2010

[14] J M Yarwood D J Bartels E M Volper and E P GreenbergldquoQuorum sensing in staphylococcus aureus biofilmsrdquo Journal ofBacteriology vol 186 no 6 pp 1838ndash1850 2004

[15] M J Eickhoff and B L Bassler ldquoSnapShot bacterial quorumsensingrdquo Cell vol 174 no 5 p 1328e1321 2018

[16] M Schuster D Joseph Sexton S P Diggle and E PeterGreenberg ldquoAcyl-homoserine lactone quorum sensing fromevolution to applicationrdquo Annual Review of Microbiology vol67 pp 43ndash63 2013

[17] MH SturmeMKleerebezem J NakayamaA D AkkermansE E Vaugha andWM DeVos ldquoCell to cell communication byautoinducing peptides in gram-positive bacteriardquo Antonie VanLeeuwenhoek vol 81 no 1ndash4 pp 233ndash243 2002

[18] C S Pereira J A Thompson and K B Xavier ldquoAI-2-mediatedsignalling in bacteriardquo FEMS Microbiology Reviews vol 37 no2 pp 156ndash181 2013

[19] M Yang K Sun L Zhou R Yang Z Zhong and J Zhu ldquoFunctional analysis of three AHL autoinducer synthase genes inMesorhizobium loti reveals the important role of quorum sens-ing in symbiotic nodulation rdquoCanadian Journal ofMicrobiologyvol 55 no 2 pp 210ndash214 2009

[20] A Ivanova K Ivanova and T Tzanov ldquoInhibition of Quorum-Sensing A New Paradigm in Controlling Bacterial Virulenceand Biofilm Formationrdquo in Biotechnological Applications ofQuorum Sensing Inhibitors V C Kalia Ed pp 5ndash10 2018

[21] Y Zeng Y Wang Z Yu and Y Huang ldquoHypersensitiveresponse of plasmid-encoded AHL synthase gene to lifestyleand nutrient by Ensifer adhaerens X097rdquo Frontiers in Microbiol-ogy vol 8 p 1160 2017

[22] A O Shpakov ldquoBacterial autoinducing peptidesrdquo Mikrobi-ologiia vol 78 no 3 pp 291ndash303 2009

[23] G J Lyon J S Wright T W Muir and R P Novick ldquoKeydeterminants of receptor activation in the agr autoinducingpeptides of Staphylococcus aureusrdquoBiochemistry vol 41 no 31pp 10095ndash10104 2002

[24] E J Murray and PWilliams ldquoDetection of agr-type autoinduc-ing peptides produced by staphylococcus aureusrdquo Methods inMolecular Biology vol 1673 pp 89ndash96 2018

[25] M J Martin S Clare D Goulding et al ldquoThe agr locus reg-ulates virulence and colonization genes in clostridium difficile027rdquo Journal of Bacteriology vol 195 no 16 pp 3672ndash3681 2013

[26] S Cheraghi L Pourgholi M Shafaati et al ldquoAnalysis ofvirulence genes and accessory gene regulator ( agr ) typesamong methicillin-resistant Staphylococcus aureus strains inIranrdquo Journal of Global Antimicrobial Resistance vol 10 pp 315ndash320 2017

[27] P Gilot G Lina T Cochard and B Poutrel ldquoAnalysis of thegenetic variability of genes encoding the RNA III-activatingcomponents Agr and TRAP in a population of Staphylococcusaureus strains isolated from cows with mastitisrdquo Journal ofClinical Microbiology vol 40 no 11 pp 4060ndash4067 2002

[28] G Lina S Jarraud G Ji et al ldquoTransmembrane topology andhistidine protein kinase activity of AgrC the agr signal receptorin Staphylococcus aureusrdquoMolecular Microbiology vol 28 no3 pp 655ndash662 1998

[29] M Guo S Gamby Y Zheng and H Sintim ldquoSmall moleculeinhibitors of AI-2 signaling in bacteria state-of-the-art andfuture perspectives for anti-quorum sensing agentsrdquo Interna-tional Journal of Molecular Sciences vol 14 no 9 pp 17694ndash17728 2013

[30] JThompson R Oliveira A Djukovic C Ubeda and K XavierldquoManipulation of the quorum sensing signal AI-2 affects theantibiotic-treated gut microbiotardquo Cell Reports vol 10 no 11pp 1861ndash1871 2015

[31] K R Hardie ldquoAutoinducer 2 activity in Escherichia coli culturesupernatants can be actively reduced despite maintenance of anactive synthase LuxSrdquoMicrobiology vol 149 no 3 pp 715ndash7282003

[32] J Wang F Li and Z Tian ldquoRole of microbiota on lunghomeostasis and diseasesrdquo Science China Life Sciences vol 60no 12 pp 1407ndash1415 2017

[33] K Riedel A Gotschlich M Givskov et al ldquoThe cep quorum-sensing system of Burkholderia cepacia H111 controls biofilmformation and swarming motilityrdquoMicrobiology vol 147 no 9pp 2517ndash2528 2001

[34] J C Linnes H Ma and J D Bryers ldquoGiant extracellular matrixbinding protein expression in staphylococcus epidermidis isregulated by biofilm formation and osmotic pressurerdquo CurrentMicrobiology vol 66 no 6 pp 627ndash633 2013

[35] AM Romanı K Fund J Artigas T Schwartz S Sabater andUObst ldquoRelevance of polymeric matrix enzymes during biofilmformationrdquoMicrobial Ecology vol 56 no 3 pp 427ndash436 2008

[36] I Kanwar A K Sah and P K Suresh ldquoBiofilm-mediatedantibiotic-resistant oral bacterial infections mechanism andcombat strategiesrdquo Current Pharmaceutical Design vol 23 no14 pp 2084ndash2095 2017

[37] S Keelara S Thakur and J Patel ldquoBiofilm formation byenvironmental isolates of Salmonella and their sensitivity tonatural antimicrobialsrdquo Foodborne Pathogens and Disease vol13 no 9 pp 509ndash516 2016

[38] F Sepandj H Ceri A Gibb R Read andMOlson ldquoMinimuminhibitory concentration versus minimum biofilm eliminating

12 BioMed Research International

concentration in evaluation of antibiotic sensitivity of entero-cocci causing peritonitisrdquo Peritoneal Dialysis International vol27 no 4 pp 464-465 2007

[39] B A Niemira and E B Solomon ldquoSensitivity of planktonicand biofilm-associated salmonella spp to ionizing radiationrdquoApplied andEnvironmentalMicrobiology vol 71 no 5 pp 2732ndash2736 2005

[40] A M Gamage G Shui M R Wenk and K L Chua ldquoN-Octanoylhomoserine lactone signalling mediated by the BpsI-BpsR quorum sensing system plays a major role in biofilmformationofBurkholderia pseudomalleirdquoMicrobiology vol 157no 4 pp 1176ndash1186 2011

[41] S H Hong M Hegde J Kim X Wang A Jayaraman andT K Wood ldquoSynthetic quorum-sensing circuit to controlconsortial biofilm formation and dispersal in a microfluidicdevicerdquo Nature Communications vol 3 p 613 2012

[42] P Sankar Ganesh and V Ravishankar Rai ldquoAttenuation ofquorum-sensing-dependent virulence factors and biofilm for-mation by medicinal plants against antibiotic resistant Pseu-domonas aeruginosardquo Journal of Traditional and Complemen-tary Medicine vol 8 no 1 pp 170ndash177 2018

[43] P Shih ldquoEffects of quorum-sensing deficiency on Pseudomonasaeruginosa biofilm formation and antibiotic resistancerdquo Journalof Antimicrobial Chemotherapy vol 49 no 2 pp 309ndash314

[44] M I Chernukha I A Shaginian IM Romanova G VMaleevand A L Gintsburg ldquoThe role of ldquoquorum sensingrdquo regula-tion system in symbiotic interaction of bacteria Burkholderiacepacia and Pseudomonas aeruginosa during mixed infectionrdquoZhurnalMikrobiologii Epidemiologii Immunobiologii no 4 pp32ndash37 2006

[45] F M Husain I Ahmad A S Al-Thubiani H H AbulreeshI M AlHazza and F Aqil ldquoLeaf extracts of Mangifera indicaL inhibit quorum sensing - Regulated production of virulencefactors and biofilm in test bacteriardquo Frontiers in Microbiologyvol 8 p 727 2017

[46] D G Renter J G Morris J M Sargeant et al ldquoPreva-lence risk factors O serogroups and virulence profiles ofshiga toxinndashproducing bacteria from cattle production environ-mentsrdquo Journal of Food Protection vol 68 no 8 pp 1556ndash15652005

[47] A R Hauser ldquoPseudomonas aeruginosa So many virulencefactors so little timerdquo Critical Care Medicine vol 39 no 9 pp2193-2194 2011

[48] R Le Berre S Nguyen E Nowak et al ldquoRelative contributionof three main virulence factors in Pseudomonas aeruginosapneumoniardquo Critical Care Medicine vol 39 no 9 pp 2113ndash2120 2011

[49] M M Gallardo-Garcia G Sanchez-Espin R Ivanova-Georgieva et al ldquoRelationship between pathogenic clinicaland virulence factors of Staphylococcus aureus in infectiveendocarditis versus uncomplicated bacteremia a case-controlstudyrdquo European Journal of Clinical Microbiology amp InfectiousDiseases vol 35 no 5 pp 821ndash828 2016

[50] F Sabouni S Mahmoudi A Bahador et al ldquoVirulence factorsof staphylococcus aureus isolates in an iranian referral childrenrsquoshospitalrdquo Osong Public Health and Research Perspectives vol 5no 2 pp 96ndash100 2014

[51] H M Aboushleib H M Omar R Abozahra A Elsheredyand K Baraka ldquoCorrelation of quorum sensing and virulencefactors in Pseudomonas aeruginosa isolates in Egyptrdquo TheJournal of Infection in Developing Countries vol 9 no 10 pp1091ndash1099 2015

[52] R T Sturbelle L F Avila T B Roos et al ldquoThe role ofquorum sensing in Escherichia coli (ETEC) virulence factorsrdquoVeterinary Microbiology vol 180 no 3-4 pp 245ndash252 2015

[53] J E Paczkowski S Mukherjee A R McCready et alldquoFlavonoids suppress Pseudomonas aeruginosa Virulencethrough allosteric inhibition of quorum-sensing receptorsrdquoTheJournal of Biological Chemistry vol 292 no 10 pp 4064ndash40762017

[54] L Weng Y Yang Y Zhang and L Wang ldquoA new syntheticligand that activatesQscRand blocks antibiotic-tolerant biofilmformation in Pseudomonas aeruginosardquo Applied Microbiologyand Biotechnology vol 98 no 6 pp 2565ndash2572 2014

[55] Y-X Yang Z-H Xu Y-Q Zhang J Tian L-X Wengand L-H Wang ldquoA new quorum-sensing inhibitor attenuatesvirulence and decreases antibiotic resistance in Pseudomonasaeruginosardquo Journal of Microbiology vol 50 no 6 pp 987ndash9932012

[56] J N Capilato S V Philippi T Reardon et al ldquoDevelopment ofa novel series of non-natural triaryl agonists and antagonists ofthe Pseudomonas aeruginosa LasR quorum sensing receptorrdquoBioorganic amp Medicinal Chemistry vol 25 no 1 pp 153ndash1652017

[57] C T OrsquoLoughlin L C Miller A Siryaporn K Drescher MF Semmelhack and B L Bassler ldquoA quorum-sensing inhibitorblocks Pseudomonas aeruginosa virulence and biofilm forma-tionrdquo Proceedings of the National Acadamy of Sciences of theUnited States of America vol 110 no 44 pp 17981ndash17986 2013

[58] G D Geske J C OrsquoNeill D M Miller M E Mattmannand H E Blackwell ldquoModulation of bacterial quorum sensingwith synthetic ligands systematic evaluation of N-acylatedhomoserine lactones in multiple species and new insights intotheir mechanisms of actionrdquo Journal of the American ChemicalSociety vol 129 no 44 pp 13613ndash13625 2007

[59] B K Khajanchi M L Kirtley S M Brackman A KChopra and B A McCormick ldquoImmunomodulatory and pro-tective roles of quorum-sensing signaling molecules N-acylhomoserine lactones during infection of mice with aeromonashydrophilardquo Infection and Immunity vol 79 no 7 pp 2646ndash2657 2011

[60] H Tomioka C Sano and Y Tatano ldquoHost-directed therapeu-tics against mycobacterial infectionsrdquo Current PharmaceuticalDesign vol 23 no 18 pp 2644ndash2656 2017

[61] M R Parsek D L Val B L Hanzelka J E Cronan Jr and EP Greenberg ldquoAcyl homoserine-lactone quorum-sensing signalgenerationrdquo Proceedings of the National Acadamy of Sciences ofthe United States of America vol 96 no 8 pp 4360ndash4365 1999

[62] MK Yadav SW Park SW Chae and J J Song ldquoSinefungin anatural nucleoside analogue of S-adenosylmethionine inhibitsStreptococcus pneumoniae biofilm growthrdquo BioMed ResearchInternational vol 2014 Article ID 156987 10 pages 2014

[63] M Hentzer and M Givskov ldquoPharmacological inhibition ofquorum sensing for the treatment of chronic bacterial infec-tionsrdquo The Journal of Clinical Investigation vol 112 no 9 pp1300ndash1307 2003

[64] V Singh G B Evans D H Lenz et al ldquoFemtomolar tran-sition state analogue inhibitors of 5rsquo-methylthioadenosineS-adenosylhomocysteine nucleosidase fromEscherichia colirdquoTheJournal of Biological Chemistry vol 280 no 18 pp 18265ndash182732005

[65] A Priyadarshi E E Kim and K Y Hwang ldquo Structuralinsights into Staphylococcus aureus enoyl-ACP reductase (FabI)

BioMed Research International 13

in complex with NADP and triclosan rdquo Proteins StructureFunction and Bioinformatics vol 78 no 2 pp 480ndash486 2010

[66] N Surolia and A Surolia ldquoTriclosan offers protection againstblood stages of malaria by inhibiting enoyl-ACP reductase ofPlasmodium falciparumrdquoNatureMedicine vol 7 no 2 pp 167ndash173 2001

[67] E Krol and A Becker ldquoRhizobial homologs of the fattyacid transporter FadL facilitate perception of long-chainacyl-homoserine lactone signalsrdquo Proceedings of the NationalAcadamy of Sciences of the United States of America vol 111 no29 pp 10702ndash10707 2014

[68] J L Copitch R N Whitehead and M A Webber ldquoPrevalenceof decreased susceptibility to triclosan in Salmonella entericaisolates fromanimals andhumans andassociationwithmultipledrug resistancerdquo International Journal of Antimicrobial Agentsvol 36 no 3 pp 247ndash251 2010

[69] S Lu N Wang S Ma X Hu L Kang and Y Yu ldquoParabensand triclosan in shellfish fromShenzhen coastal waters bioindi-cation of pollution and human health risksrdquo EnvironmentalPollution vol 246 pp 257ndash263 2018

[70] N Huma P Shankar J Kushwah et al ldquoDiversity and poly-morphism in AHL-Lactonase gene (aiiA) of Bacillusrdquo Journalof Microbiology and Biotechnology vol 21 no 10 pp 1001ndash10112011

[71] S Y Park B J Hwang M Shin J Kim H Kim and J LeeldquoN-acylhomoserine lactonase-producingRhodococcussppwithdifferent AHL-degrading activitiesrdquo FEMSMicrobiology Lettersvol 261 no 1 pp 102ndash108 2006

[72] A Guendouze L Plener J Bzdrenga et al ldquoEffect of quo-rum quenching lactonase in clinical isolates of pseudomonasaeruginosa and comparison with quorum sensing inhibitorsrdquoFrontiers in Microbiology vol 8 p 227 2017

[73] S Hraiech J Hiblot J Lafleur et al ldquoInhaled lactonase reducespseudomonas aeruginosa quorum sensing and mortality in ratpneumoniardquo PLoS ONE vol 9 no 10 Article ID e107125 2014

[74] J Y Chow Y Yang S B Tay K L Chua and W S YewldquoDisruption of biofilm formation by the human pathogenacinetobacter baumannii using engineered quorum-quenchinglactonasesrdquoAntimicrobial Agents andChemotherapy vol 58 no3 pp 1802ndash1805 2014

[75] X FanM Liang L Wang R Chen H Li and X Liu ldquoAii810 anovel cold-adapted N-acylhomoserine lactonase discovered inametagenome can strongly attenuate Pseudomonas aeruginosavirulence factors and biofilm formationrdquo Frontiers in Microbiol-ogy vol 8 p 1950 2017

[76] MM Sakr KM AboshanabW F ElkhatibMA Yassien andN AHassouna ldquoOverexpressed recombinant quorumquench-ing lactonase reduces the virulence motility and biofilm for-mationofmultidrug-resistant Pseudomonas aeruginosa clinicalisolatesrdquo Appl Microbiol Biotechnol vol 102 no 24 pp 10613ndash10622 2018

[77] C Schipper C Hornung P Bijtenhoorn M Quitschau SGrond andW R Streit ldquoMetagenome-derived clones encodingtwo novel lactonase family proteins involved in biofilm inhibi-tion in pseudomonas aeruginosardquo Applied and EnvironmentalMicrobiology vol 75 no 1 pp 224ndash233 2008

[78] W Dong J Zhu X Guo et al ldquoCharacterization of AiiKan AHL lactonase from Kurthia huakui LAM0618T and itsapplication in quorum quenching on Pseudomonas aeruginosaPAO1rdquo Scientific Reports vol 8 no 1 p 6013 2018

[79] W Liu C Ran Z Liu et al ldquoEffects of dietary Lactobacillusplantarum and AHL lactonase on the control of Aeromonas

hydrophila infection in tilapiardquoMicrobiologyopen vol 5 no 4pp 687ndash699 2016

[80] M Torres J C Reina J C Fuentes-Monteverde et al ldquoAHL-lactonase expression in three marine emerging pathogenicVibrio spp reduces virulence and mortality in brine shrimp(Artemia salina) and Manila clam (Venerupis philippinarum)rdquoPLoS ONE vol 13 no 4 Article ID e0195176 2018

[81] G Vinoj B Vaseeharan S Thomas A J Spiers and S ShanthildquoQuorum-quenching activity of the AHL-lactonase from bacil-lus licheniformis DAHB1 inhibits vibrio biofilm formation invitro and reduces shrimp intestinal colonisation andmortalityrdquoMarine Biotechnology vol 16 no 6 pp 707ndash715 2014

[82] V C Kalia ldquoIn search of versatile organisms for quorum-sensing inhibitors acyl homoserine lactones (AHL)-acylaseand AHL-lactonaserdquo FEMS Microbiology Letters vol 359 no2 p 143 2014

[83] V B Maisuria and A S Nerurkar ldquoInterference of quorumsensing by Delftia sp VM4 depends on the activity of a noveln-acylhomoserine lactone-acylaserdquo PLoS ONE vol 10 no 9Article ID e0138034 2015

[84] R Mukherji N K Varshney P Panigrahi C Suresh and APrabhune ldquoA new role for penicillin acylases degradation ofacyl homoserine lactone quorum sensing signals by Kluyveracitrophila penicillin G acylaserdquo Enzyme and Microbial Technol-ogy vol 56 pp 1ndash7 2014

[85] C F Sio L G Otten R H Cool et al ldquoQuorum quenchingby an N-acyl-homoserine lactone acylase from Pseudomonasaeruginosa PAO1rdquo Infection and Immunity vol 74 no 3 pp1673ndash1682 2006

[86] K Ivanova M M Fernandes E Mendoza and T TzanovldquoEnzyme multilayer coatings inhibit Pseudomonas aeruginosabiofilm formation on urinary cathetersrdquo Applied Microbiologyand Biotechnology vol 99 no 10 pp 4373ndash4385 2015

[87] N Grover J G Plaks S R Summers G R Chado M J Schurrand J L Kaar ldquoAcylase-containing polyurethane coatings withanti-biofilm activityrdquo Biotechnology and Bioengineering vol 113no 12 pp 2535ndash2543 2016

[88] J Lee I Lee J Nam D S Hwang K-M Yeon and JKim ldquoImmobilization and stabilization of acylase on carboxy-lated polyaniline nanofibers for highly effective antifoulingapplication via quorum quenchingrdquo ACS Applied Materials ampInterfaces vol 9 no 18 pp 15424ndash15432 2017

[89] S Uroz S R Chhabra M Camara P Williams P Ogerand Y Dessaux ldquoN-acylhomoserine lactone quorum-sensingmolecules are modified and degraded by Rhodococcus ery-thropolis W2 by both amidolytic and novel oxidoreductaseactivitiesrdquoMicrobiology vol 151 no 10 pp 3313ndash3322 2005

[90] B Eva and S Maria ldquoMicrobial secondary metabolites asinhibitors of pharmaceutically important transferases and oxi-doreductasesrdquo Ceska Slov Farm vol 61 no 3 pp 107ndash114 2012

[91] P Bijtenhoorn H Mayerhofer J Muller-Dieckmann et alldquoA novel metagenomic Short-Chain dehydrogenasereductaseattenuates pseudomonas Aeruginosa biofilm formation andvirulence on Caenorhabditis elegansrdquo PLoS ONE vol 6 no 10Article ID e26278 2011

[92] J D Wildschut R M Lang J K Voordouw and G Voor-douw ldquoRubredoxin oxygen oxidoreductase enhances survivalof desulfovibrio vulgaris hildenborough under microaerophilicconditionsrdquo Journal of Bacteriology vol 188 no 17 pp 6253ndash6260 2006

14 BioMed Research International

[93] X Zhang S Ou-yang JWang L Liao RWu and JWei ldquoCon-struction of antibacterial surface via layer-by-layer methodrdquoCurrent Pharmaceutical Design vol 24 no 8 pp 926ndash935 2018

[94] C Pustelny A Albers K Buldt-Karentzopoulos et al ldquoDiox-ygenase-mediated quenching of quinolone-dependent quorumsensing in pseudomonas aeruginosardquoChemistry amp Biology vol16 no 12 pp 1259ndash1267 2009

[95] J T Hodgkinson W R Galloway M Welch and DR Spring ldquoMicrowave-assisted preparation of the quorum-sensing molecule 2-heptyl-3-hydroxy-4(1H)-quinolone andstructurally related analogsrdquo Nature Protocols vol 7 no 6 pp1184ndash1192 2012

[96] F Witzgall T Depke M Hoffmann et al ldquoThe alkylquinolonerepertoire of Pseudomonas aeruginosa is linked to structuralflexibility of the fabh-like 2-heptyl-3-hydroxy-4(1H)-quinolone(PQS) biosynthesis enzyme PqsBCrdquo ChemBioChem vol 19 no14 pp 1531ndash1544 2018

[97] L Andresen E Sala V Koiv and A Mae ldquoA role for theRcs phosphorelay in regulating expression of plant cell walldegrading enzymes in Pectobacterium carotovorum subspcarotovorumrdquoMicrobiology vol 156 no 5 pp 1323ndash1334 2010

[98] L Andresen V Koiv T Alamae and A Mae ldquoThe Rcs phos-phorelay modulates the expression of plant cell wall degradingenzymes and virulence in Pectobacterium carotovorum sspcarotovorumrdquo FEMS Microbiology Letters vol 273 no 2 pp229ndash238 2007

[99] R K Gupta S Chhibber and K Harjai ldquoAcyl homoserinelactones from culture supernatants of pseudomonas aeruginosaaccelerate host immunomodulationrdquo PLoS ONE vol 6 no 6Article ID e20860 2011

[100] G F Kaufmann J Park J M Mee R J Ulevitch and KD Janda ldquoThe quorum quenching antibody RS2-1G9 protectsmacrophages from the cytotoxic effects of the Pseudomonasaeruginosa quorum sensing signalling molecule N-3-oxo-dodecanoyl-homoserine lactonerdquo Molecular Immunology vol45 no 9 pp 2710ndash2714 2008

[101] S Koul J Prakash A Mishra and V C Kalia ldquoPotential emer-gence of multi-quorum sensing inhibitor resistant (MQSIR)bacteriardquo Indian Journal of Microbiology vol 56 no 1 pp 1ndash182016

[102] T Praneenararat A G Palmer and H E Blackwell ldquoChemicalmethods to interrogate bacterial quorum sensing pathwaysrdquoOrganicampBiomolecular Chemistry vol 10 no 41 pp 8189ndash81992012

[103] J Park R Jagasia G F Kaufmann et al ldquoInfection controlby antibody disruption of bacterial quorum sensing signalingrdquoChemistry amp Biology vol 14 no 10 pp 1119ndash1127 2007

[104] C Grandclement M Tannieres S Morera Y Dessaux DFaure andM Camara ldquoQuorum quenching role in nature andapplied developmentsrdquo FEMSMicrobiology Reviews vol 40 no1 pp 86ndash116 2016

[105] MHan J GuG F Gao andW J Liu ldquoChina in action nationalstrategies to combat against emerging infectious diseasesrdquoScience China Life Sciences vol 60 no 12 pp 1383ndash1385 2017

[106] J Liu H Yu Y Huang et al ldquoComplete genome sequence ofa novel bacteriophage infecting Bradyrhizobium diazoefficiensUSDA110rdquo Science China Life Sciences vol 61 no 1 pp 118ndash1212018

[107] L D Christensen M van Gennip T H Jakobsen et alldquoSynergistic antibacterial efficacy of early combination treat-ment with tobramycin and quorum-sensing inhibitors against

Pseudomonas aeruginosa in an intraperitoneal foreign-bodyinfection mouse modelrdquo Journal of Antimicrobial Chemother-apy vol 67 no 5 pp 1198ndash1206 2012

[108] J Fong M Yuan T H Jakobsen et al ldquoDisulfide bond-containing ajoene analogues as novel quorum sensinginhibitors of Pseudomonas aeruginosardquo Journal of MedicinalChemistry vol 60 no 1 pp 215ndash227 2017

[109] R Garcıa-Contreras M Martınez-Vazquez N VelazquezGuadarrama et al ldquo Resistance to the quorum-quenchingcompounds brominated furanone C-30 and 5-fluorouracil inPseudomonas aeruginosa clinical isolates rdquo Pathogens and Dis-ease vol 68 no 1 pp 8ndash11 2013

[110] T H Jakobsen S K Bragason R K Phipps et al ldquoFood as asource for quorum sensing inhibitors iberin from horseradishrevealed as a quorum sensing inhibitor of pseudomonas aerug-inosardquo Applied and Environmental Microbiology vol 78 no 7pp 2410ndash2421 2012

[111] A Vadekeetil H Saini S Chhibber and K Harjai ldquo Exploitingthe antivirulence efficacy of an ajoene-ciprofloxacin combina-tion against Pseudomonas aeruginosa biofilm associatedmurineacute pyelonephritis rdquo Biofouling vol 32 no 4 pp 371ndash3822016

[112] S Bahari H Zeighami H Mirshahabi S Roudashti and FHaghi ldquoInhibition of pseudomonas aeruginosa quorum sensingby subinhibitory concentrations of curcumin with gentamicinand azithromycinrdquo Journal of Global Antimicrobial Resistancevol 10 pp 21ndash28 2017

[113] A S Roccaro A R Blanco F Giuliano D Rusciano and VEnea ldquoEpigallocatechin-gallate enhances the activity of tetra-cycline in staphylococci by inhibiting its efflux from bacterialcellsrdquo Antimicrobial Agents and Chemotherapy vol 48 no 6pp 1968ndash1973 2004

[114] C Chu J Deng Y Man and Y Qu ldquoGreen tea extractsepigallocatechin-3-gallate for different treatmentsrdquo BioMedResearch International vol 2017 Article ID 5615647 9 pages2017

[115] A Furiga B Lajoie S El Hage G Baziard and C RoquesldquoImpairment of pseudomonas aeruginosa biofilm resistance toantibiotics by combining the drugs with a new quorum-sensinginhibitorrdquo Antimicrobial Agents and Chemotherapy vol 60 no3 pp 1676ndash1686 2016

[116] Y Inoue N Togashi and H Hamashima ldquoFarnesol-induceddisruption of the staphylococcus aureus cytoplasmic mem-branerdquo Biological and Pharmaceutical Bulletin vol 39 no 5 pp653ndash656 2016

[117] C Kim D Hesek M Lee and S Mobashery ldquoPotentiationof the activity of beta-lactam antibiotics by farnesol and itsderivativesrdquo Bioorganic amp Medicinal Chemistry Letters vol 28no 4 pp 642ndash645 2018

[118] G Brackman P Cos L Maes H J Nelis and T Coenye ldquoQuo-rum sensing inhibitors increase the susceptibility of bacterialbiofilms to antibiotics in vitro and in vivordquoAntimicrobial Agentsand Chemotherapy vol 55 no 6 pp 2655ndash2661 2011

[119] G Brackman K Breyne R De Rycke et al ldquoThe quorum sens-ing inhibitor hamamelitannin increases antibiotic susceptibilityof staphylococcus aureus biofilms by affecting peptidoglycanbiosynthesis and eDNA releaserdquo Scientific Reports vol 6 ArticleID 20321 2016

[120] J M Walz R L Avelar K J Longtine K L Carter L A Mer-mel and S O Heard ldquoAnti-infective external coating of centralvenous catheters A randomized noninferiority trial comparing

BioMed Research International 15

5-fluorouracil with chlorhexidinesilver sulfadiazine in pre-venting catheter colonizationrdquo Critical Care Medicine vol 38no 11 pp 2095ndash2102 2010

[121] C van Delden T Kohler F Brunner-Ferber B Francois JCarlet and J Pechere ldquoAzithromycin to prevent Pseudomonasaeruginosa ventilator-associated pneumonia by inhibition ofquorum sensing a randomized controlled trialrdquo Intensive CareMedicine vol 38 no 7 pp 1118ndash1125 2012

[122] A R Smyth P M Cifelli C A Ortori et al ldquoGarlic asan inhibitor of Pseudomonas aeruginosa quorum sensing incystic fibrosisndasha pilot randomized controlled trialrdquo PediatricPulmonology vol 45 no 4 pp 356ndash362 2010

Hindawiwwwhindawicom

International Journal of

Volume 2018

Zoology

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Anatomy Research International

PeptidesInternational Journal of

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Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

The Scientific World Journal

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Hindawiwwwhindawicom Volume 2018

BioinformaticsAdvances in

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Hindawiwwwhindawicom Volume 2018

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Cell BiologyInternational Journal of

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Hindawiwwwhindawicom Volume 2018

Biochemistry Research International

ArchaeaHindawiwwwhindawicom Volume 2018

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International Journal of

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Nucleic AcidsJournal of

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Submit your manuscripts atwwwhindawicom

BioMed Research International 7

Table4Ap

plications

involvingwith

AHLs

degradationby

anti-QSa

gents3-oxo-C1

2N-3-oxodo

decano

yl-H

SLA

HLN-acyl-h

omoserinelactonesC4

-LHLbu

tenylhom

oserinelactones

C6-LHL

hexano

ylho

moserinelactones

Objectiv

esStrains

Anti-Q

Sagents

Target

Effects

Ref

Tilapia

Aeromonas

hydrophila

AHLlacton

aseA

IO6

Degradatio

nof

thea

cyl-h

omoserinelactones

Maintainedthem

icrovilli

leng

thin

theforegut

oftilapiabut

significantly

lowe

rthanthoseo

fthe

control

[79]

Shrim

pandclam

Vibriona

ceae

strains

Deletionof

AHLs

genesin

34marineV

ibrio

naceae

strains

Acyl-hom

oserinelactonesinactivation

Redu

cedvirulencea

ndmortalityof

them

utant

strains

inbrines

hrim

pandManila

clam

[80]

Shrim

pVibrio

parahaem

olyticu

sAHL-lacton

ase

(AiiA

)Degradatio

nof

thea

cyl-h

omoserinelactones

Inhibitedvibrio

biofi

lmdevelopm

entand

attenu

ated

infectionandmortalityRe

duce

vibrio

viablecoun

tsandbiofi

lmdevelopm

entintheintestin

e[81]

Enzymem

ultilayer

coatings

Chromobacteriu

mviolaceum

CECT

5999Pseud

omonas

aerugin

osaAT

CC

10145

Acylasefrom

Aspergillus

melleus

Degradatio

nof

C6-LHL

Inhibited50violaceinprod

uctio

nby

Chromobacteriu

mviolaceum

CECT

5999R

educes

theP

seud

omonas

aerugin

osaAT

CC10145b

iofilm

form

ationun

derstatic

anddynamiccond

ition

s

[86]

Acylase-containing

polyurethane

coatings

Pseudomonas

aerugin

osaAT

CC

10145a

ndPA

O1

Acylasefrom

Aspergillus

melleus

Degradatio

nof

C4-LHL

C6-LHL

and

3-oxo-C1

2-LH

L

Immob

ilizatio

nof

acylaseled

toan

approxim

ately

60redu

ctionin

biofi

lmform

ation

redu

cethe

secretionof

pyocyanin

[87]

Immob

ilizatio

non

Nanofi

bers

Pseudomonas

aerugin

osaPA

O1

Acylase(EC

35114)

Degradatio

nof

AHLindu

cers

Redu

cedtheb

iofilmbiofoulingform

ationun

der

static

andcontinuo

usflo

wcond

ition

s[88]

8 BioMed Research International

Table5Stud

iesd

emon

stratingQSdisrup

tionby

antib

odiestargetin

g

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

In-vitroandRA

W2647cells

Pseudomonas

aerugin

osa

Antibod

yRS2-1G9

generatedagainsta

3-oxo-do

decano

ylho

moserinelactone

analog

hapten

Targetingtheb

acteria

lN-3-oxo-dod

ecanoyl

homoserinelactone

molecules

Protectm

urineb

onem

arrow-derived

macroph

ages

from

thec

ytotoxiceffectsandalso

preventedthe

activ

ationof

them

itogen-activ

ated

proteinkinase

p38

[100]

In-vitro

Pseudomonas

aerugin

osa

Antibod

yXYD

-11G

2Hydrolyzing

N-3-(oxod

odecanoyl)-L-ho

moserine

lacton

eSupp

ressed

QSsig

nalin

g[101]

In-vitroandmou

semod

elStaphylococcus

aureus

Antibod

yAP4

-24H

11elicitedagainsta

ratio

nally

desig

nedhapten

Sequ

estrationof

thea

utoind

ucingp

eptid

e-4

Supp

ressed

Saureus

pathogenicity

inan

abscess

form

ationmou

semod

elin

vivo

andprovided

completep

rotectionagainsta

lethalStaphylococcus

aureus

challenge

[103]

BioMed Research International 9

Table6Stud

iesd

emon

stratingthes

ynergistice

ffectso

fanti-Q

Sagentsandantib

iotic

s

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

Mice

Pseudomonas

aerugin

osa

Furano

neC-

30ajoeneo

rho

rseradish

juicee

xtractin

Com

binatio

ncurcum

in

QSinhibitio

nenhancethe

sensitivity

ofpathogen

toantib

iotic

sRe

sultedin

anincreasedclearanceo

fPseud

omonas

aerugin

osain

aforeign

-bod

yinfectionmod

el

[107]

In-vitro

Pseudomonas

aerugin

osa

with

tobram

ycin

gentam

icin

and

azith

romycin

Indu

cedconcentrations

ofC1

2-ho

moserine

lacton

eand

C4-h

omoserinelactone

Curcum

inshow

edsynergisticeffectswith

azith

romycin

andgentam

icinC

ombinatio

nuse

redu

cedQS-relatedvirulencefactors

Dow

nregulated

QS-relatedgenes

[112]

In-vitro

Staphylococci

Epigallocatechin-3-gallate

with

Tetracyclin

eInhibitio

nof

thea

ctivity

ofTet(K

)pum

pseffl

uxpu

mps

ofad

ifferentclassTet(B

)En

hanced

theb

acteric

idaleffecto

fTetracyclineo

nStaphylococci

[113]

In-vitro

Pseudomonas

aerugin

osa

N-(2-pyrim

idyl)

butanamideC1

1Dow

nregulationof

rhlrhlA

andlasB

genes

Increasedthes

usceptibilityto

antib

iotic

sand

attenu

ated

thep

atho

genicityof

theb

acteriu

m

[115]

In-vitro

Staphylococcus

aureus

(methicillin-resistant

Sau

reus)

Farnesolwith120573-la

ctam

antib

iotic

s

Inhibitio

nof

lipasea

ctivity

anddisrup

tionof

thec

ytop

lasm

icmem

branethrou

ghthe

leakageo

fpotassiu

mions

Attenu

ated

ther

ateo

fgrowth

ofbacteriaand

coun

terin

gub

iquitous120573-la

ctam

resistancein

bacteria

[116117]

In-vitro

Cele

gansG

aller

iamellonellamice

Burkholderia

cenocepacia

Staphylococcus

aureus

Escherich

iacoli

Baicalin

hydrate

cinn

amaldehyde

hamam

elitann

inwith

Tobram

ycinvancomycin

andclindamycin

Inhibitio

nof

biofi

lmform

ation

QSinhibitio

nenhancethe

sensitivity

ofpathogen

toantib

iotic

s

Com

bining

theu

seof

antib

odyandanti-QSagents

increasedsusceptib

ilityof

theb

acteria

tothe

antib

iotic

and

increasedho

stsurvivalrateaft

erinfection

[118]

10 BioMed Research International

al found in their study [100] that the antibody RS2-1G9can bind to 3-oxo-C12-HSL in the extracellular environmentof Pseudomonas aeruginosa thereby attenuating the inflam-matory response of the host XYD-11G2 antibody has beenshown to catalyze the hydrolysis of 3-oxo-C12-HSL signalingthus inhibiting the pyocyanin production by Gram-negativebacteria [101 102] The monoclonal antibody AP4-24H11 wasfound to block the QS signal of Gram-positive Staphylococcusaureus by interfering with AIP IV [103] Another in vivo studyshowed that the antibody AP4-24H11 could significantlyattenuate the tissue necrosis in the infected model [104]Although these monoclonal antibodies have been identifiedto block the QS signaling of pathogenic bacteria (Table 5)their applications for treating bacterial diseases are still in theinitial stage

45 Combinations of Anti-QS Agents and Antibiotics Com-bining use of antibiotic with an anti-QS agent is the mosteffective clinical strategy for the treatment of bacterial dis-eases at present [105 106] Many studies have confirmed thesynergistic effect of antibiotics and anti-QS agents (Table 6)Ajoene furanone c-30 and horseradish extract have beenrevealed to reduce the expression of virulence factors inPseudomonas aeruginosa and make Pseudomonas aeruginosaeasier to be cleared by tobramycin [107ndash111] Another studyhas confirmed the synergistic effects of curcumin gentam-icin and azithromycin on Pseudomonas aeruginosa that isthe expressions of virulence genes were significantly down-regulated by the combining use of curcumin together withgentamicin or azithromycin and the therapeutic doses ofgentamicin and azithromycin were minimized by curcuminsupplementation [112] The anti-QS compounds such asgallocatechin 3-gallate and caffeic acid enhanced therapeuticeffects on Mycoplasma pneumoniae infection by combininguse with tetracycline ciprofloxacin or gentamicin [113 114]N-(2-pyrimidyl) butylamine was confirmed to enhance theantibacterial effect of tobramycin colistin and ciprofloxacinon Pseudomonas aeruginosa [115] Recent studies [116 117]have shown that both farnesol and hamamelitannin canreduce the virulence of Staphylococcus aureus and increasethe sensitivity of Staphylococcus aureus to 120573-lactam antibi-otics Synergistic effects of hamamelitannin baicalin hydratecinnamaldehyde and antibiotics have been demonstrated indifferent infection models [118 119]These findings imply thatcombining use of antibiotics with ant-QS agents has greattherapeutic potential for bacterial diseases

5 Conclusions

Regulating bacterial QS signaling by QS-targeted agents isan effective strategy to control the production of bacte-rial virulence factors and the formation of biofilm Thisnovel nonantibiotic therapy can inhibit the expression ofpathogenic genes prevent infection and reduce the riskof drug resistance of bacterial cells and has been widelyexploited in recent years A large number of studies haveidentified many anti-QS agents to control the pathogenicphenotypes ofmost bacteria and to attenuate the pathological

damage in various animal infection models However mostanti-QS agents are still in the preclinical phase and morehuman clinical trials are warranted to test their practicalfeasibility The results of several existing clinical studies [120ndash122] on anti-QS agents show that compared with antibioticsthe anti-QS compounds may have potential toxicity andtheir therapeutic effect is not as stable as that of antibioticswhich limited their extensive application Combining use ofanti-QS agents with conventional antibiotics can significantlyimprove the efficacy of therapeutic drugs and decrease thecost of human healthcare and is likely to be the mainapplication method of anti-QS agents for bacterial diseasestreatment in the future

Conflicts of Interest

The authors declare that there are no conflicts of interestregarding the publication of this paper

Acknowledgments

The authors are thankful to the China Scholarship Council(CSC) for both financial support and scholarships Theauthors appreciate Dr Ruiqiang Yang at the Nanjing Agri-culture University for his help on this review This workwas supported by the National Natural Science Foundationof China (31472107) the Youth Science Fund Project of theNational Natural Science Foundation of China (31702126)the Chinese Academy of Sciences lsquoHundred Talentrsquo awardthe National Science Foundation for Distinguished YoungScholars of Hunan Province (2016JJ1015) the Postgradu-ate Research and Innovation Project of Hunan Province(CX2017B348) the Hunan Province ldquoHunan Young Scienceand Technology Innovation Talentrdquo Project (2015RS4053)the Hunan Agricultural University Provincial Outstand-ing Doctoral Dissertation Cultivating Fund (YB2017002)and the Open Foundation of Key Laboratory of Agro-ecological Processes in Subtropical Region Institute ofSubtropical Agriculture Chinese Academy of Sciences(ISA2016101)

References

[1] M Etminan B Carleton J A C Delaney and R PadwalldquoAntibiotics ineffective for prevention of recurrentMIrdquo Journalof Family Practice vol 53 no 7 p 525 2004

[2] F E Akram T El-Tayeb K Abou-Aisha and M El-AzizildquoA combination of silver nanoparticles and visible blue lightenhances the antibacterial efficacy of ineffective antibioticsagainst methicillin-resistant Staphylococcus aureus (MRSA)rdquoAnnals of Clinical Microbiology and Antimicrobials vol 15 no1 p 48 2016

[3] L A Barton and M W Simon ldquoProphylactic antibioticsIneffective or inefficaciousrdquo Clinical Pediatrics vol 53 no 8 p813 2014

[4] J Neumaier ldquoAntibiotics are up to 90 ineffective what reallyhelps in common coldsrdquo MMWmdashFortschritte der Medizin vol153 no 3 pp 18-19 2011

BioMed Research International 11

[5] B Schlemmer ldquoBetter prescribing of antibiotics Preventing therisk of ineffective treatment in current infectionrdquo La Revue dupraticien vol 53 no 14 pp 1525-1526 2003

[6] P Stiefelhagen ldquoSuspected severe pneumonia Antibiotics areineffective - what nowrdquo MMWmdashFortschritte der Medizin vol157 no 17 p 28 2015

[7] Z Li and M Knetsch ldquoAntibacterial strategies for wounddressing preventing infection and stimulating healingrdquoCurrentPharmaceutical Design vol 24 no 8 pp 936ndash951 2018

[8] W Xu S Dong Y Han S Li and Y Liu ldquoHydrogels asantibacterial biomaterialsrdquo Current Pharmaceutical Design vol24 no 8 pp 843ndash854 2018

[9] ldquoMicrobiology by numbersrdquo Nature Reviews Microbiology vol9 no 9 p 628 2011

[10] J P Pearson E C Pesci and B H Iglewski ldquoRoles of Pseu-domonas aeruginosa las and rhl quorum-sensing systems incontrol of elastase and rhamnolipid biosynthesis genesrdquo Journalof Bacteriology vol 179 no 18 pp 5756ndash5767 1997

[11] C Van Delden E C Pesci J P Pearson and B H IglewskildquoStarvation selection restores elastase and rhamnolipid produc-tion in a Pseudomonas aeruginosa quorum-sensing mutantrdquoInfection and Immunity vol 66 no 9 pp 4499ndash4502 1998

[12] L E Dietrich A Price-Whelan A Petersen M Whiteley andD K Newman ldquoThe phenazine pyocyanin is a terminal sig-nalling factor in the quorum sensing network of Pseudomonasaeruginosardquo Molecular Microbiology vol 61 no 5 pp 1308ndash1321 2006

[13] E C Carnes D M Lopez N P Donegan et al ldquoConfinement-induced quorum sensing of individual Staphylococcus aureusbacteriardquoNature Chemical Biology vol 6 no 1 pp 41ndash45 2010

[14] J M Yarwood D J Bartels E M Volper and E P GreenbergldquoQuorum sensing in staphylococcus aureus biofilmsrdquo Journal ofBacteriology vol 186 no 6 pp 1838ndash1850 2004

[15] M J Eickhoff and B L Bassler ldquoSnapShot bacterial quorumsensingrdquo Cell vol 174 no 5 p 1328e1321 2018

[16] M Schuster D Joseph Sexton S P Diggle and E PeterGreenberg ldquoAcyl-homoserine lactone quorum sensing fromevolution to applicationrdquo Annual Review of Microbiology vol67 pp 43ndash63 2013

[17] MH SturmeMKleerebezem J NakayamaA D AkkermansE E Vaugha andWM DeVos ldquoCell to cell communication byautoinducing peptides in gram-positive bacteriardquo Antonie VanLeeuwenhoek vol 81 no 1ndash4 pp 233ndash243 2002

[18] C S Pereira J A Thompson and K B Xavier ldquoAI-2-mediatedsignalling in bacteriardquo FEMS Microbiology Reviews vol 37 no2 pp 156ndash181 2013

[19] M Yang K Sun L Zhou R Yang Z Zhong and J Zhu ldquoFunctional analysis of three AHL autoinducer synthase genes inMesorhizobium loti reveals the important role of quorum sens-ing in symbiotic nodulation rdquoCanadian Journal ofMicrobiologyvol 55 no 2 pp 210ndash214 2009

[20] A Ivanova K Ivanova and T Tzanov ldquoInhibition of Quorum-Sensing A New Paradigm in Controlling Bacterial Virulenceand Biofilm Formationrdquo in Biotechnological Applications ofQuorum Sensing Inhibitors V C Kalia Ed pp 5ndash10 2018

[21] Y Zeng Y Wang Z Yu and Y Huang ldquoHypersensitiveresponse of plasmid-encoded AHL synthase gene to lifestyleand nutrient by Ensifer adhaerens X097rdquo Frontiers in Microbiol-ogy vol 8 p 1160 2017

[22] A O Shpakov ldquoBacterial autoinducing peptidesrdquo Mikrobi-ologiia vol 78 no 3 pp 291ndash303 2009

[23] G J Lyon J S Wright T W Muir and R P Novick ldquoKeydeterminants of receptor activation in the agr autoinducingpeptides of Staphylococcus aureusrdquoBiochemistry vol 41 no 31pp 10095ndash10104 2002

[24] E J Murray and PWilliams ldquoDetection of agr-type autoinduc-ing peptides produced by staphylococcus aureusrdquo Methods inMolecular Biology vol 1673 pp 89ndash96 2018

[25] M J Martin S Clare D Goulding et al ldquoThe agr locus reg-ulates virulence and colonization genes in clostridium difficile027rdquo Journal of Bacteriology vol 195 no 16 pp 3672ndash3681 2013

[26] S Cheraghi L Pourgholi M Shafaati et al ldquoAnalysis ofvirulence genes and accessory gene regulator ( agr ) typesamong methicillin-resistant Staphylococcus aureus strains inIranrdquo Journal of Global Antimicrobial Resistance vol 10 pp 315ndash320 2017

[27] P Gilot G Lina T Cochard and B Poutrel ldquoAnalysis of thegenetic variability of genes encoding the RNA III-activatingcomponents Agr and TRAP in a population of Staphylococcusaureus strains isolated from cows with mastitisrdquo Journal ofClinical Microbiology vol 40 no 11 pp 4060ndash4067 2002

[28] G Lina S Jarraud G Ji et al ldquoTransmembrane topology andhistidine protein kinase activity of AgrC the agr signal receptorin Staphylococcus aureusrdquoMolecular Microbiology vol 28 no3 pp 655ndash662 1998

[29] M Guo S Gamby Y Zheng and H Sintim ldquoSmall moleculeinhibitors of AI-2 signaling in bacteria state-of-the-art andfuture perspectives for anti-quorum sensing agentsrdquo Interna-tional Journal of Molecular Sciences vol 14 no 9 pp 17694ndash17728 2013

[30] JThompson R Oliveira A Djukovic C Ubeda and K XavierldquoManipulation of the quorum sensing signal AI-2 affects theantibiotic-treated gut microbiotardquo Cell Reports vol 10 no 11pp 1861ndash1871 2015

[31] K R Hardie ldquoAutoinducer 2 activity in Escherichia coli culturesupernatants can be actively reduced despite maintenance of anactive synthase LuxSrdquoMicrobiology vol 149 no 3 pp 715ndash7282003

[32] J Wang F Li and Z Tian ldquoRole of microbiota on lunghomeostasis and diseasesrdquo Science China Life Sciences vol 60no 12 pp 1407ndash1415 2017

[33] K Riedel A Gotschlich M Givskov et al ldquoThe cep quorum-sensing system of Burkholderia cepacia H111 controls biofilmformation and swarming motilityrdquoMicrobiology vol 147 no 9pp 2517ndash2528 2001

[34] J C Linnes H Ma and J D Bryers ldquoGiant extracellular matrixbinding protein expression in staphylococcus epidermidis isregulated by biofilm formation and osmotic pressurerdquo CurrentMicrobiology vol 66 no 6 pp 627ndash633 2013

[35] AM Romanı K Fund J Artigas T Schwartz S Sabater andUObst ldquoRelevance of polymeric matrix enzymes during biofilmformationrdquoMicrobial Ecology vol 56 no 3 pp 427ndash436 2008

[36] I Kanwar A K Sah and P K Suresh ldquoBiofilm-mediatedantibiotic-resistant oral bacterial infections mechanism andcombat strategiesrdquo Current Pharmaceutical Design vol 23 no14 pp 2084ndash2095 2017

[37] S Keelara S Thakur and J Patel ldquoBiofilm formation byenvironmental isolates of Salmonella and their sensitivity tonatural antimicrobialsrdquo Foodborne Pathogens and Disease vol13 no 9 pp 509ndash516 2016

[38] F Sepandj H Ceri A Gibb R Read andMOlson ldquoMinimuminhibitory concentration versus minimum biofilm eliminating

12 BioMed Research International

concentration in evaluation of antibiotic sensitivity of entero-cocci causing peritonitisrdquo Peritoneal Dialysis International vol27 no 4 pp 464-465 2007

[39] B A Niemira and E B Solomon ldquoSensitivity of planktonicand biofilm-associated salmonella spp to ionizing radiationrdquoApplied andEnvironmentalMicrobiology vol 71 no 5 pp 2732ndash2736 2005

[40] A M Gamage G Shui M R Wenk and K L Chua ldquoN-Octanoylhomoserine lactone signalling mediated by the BpsI-BpsR quorum sensing system plays a major role in biofilmformationofBurkholderia pseudomalleirdquoMicrobiology vol 157no 4 pp 1176ndash1186 2011

[41] S H Hong M Hegde J Kim X Wang A Jayaraman andT K Wood ldquoSynthetic quorum-sensing circuit to controlconsortial biofilm formation and dispersal in a microfluidicdevicerdquo Nature Communications vol 3 p 613 2012

[42] P Sankar Ganesh and V Ravishankar Rai ldquoAttenuation ofquorum-sensing-dependent virulence factors and biofilm for-mation by medicinal plants against antibiotic resistant Pseu-domonas aeruginosardquo Journal of Traditional and Complemen-tary Medicine vol 8 no 1 pp 170ndash177 2018

[43] P Shih ldquoEffects of quorum-sensing deficiency on Pseudomonasaeruginosa biofilm formation and antibiotic resistancerdquo Journalof Antimicrobial Chemotherapy vol 49 no 2 pp 309ndash314

[44] M I Chernukha I A Shaginian IM Romanova G VMaleevand A L Gintsburg ldquoThe role of ldquoquorum sensingrdquo regula-tion system in symbiotic interaction of bacteria Burkholderiacepacia and Pseudomonas aeruginosa during mixed infectionrdquoZhurnalMikrobiologii Epidemiologii Immunobiologii no 4 pp32ndash37 2006

[45] F M Husain I Ahmad A S Al-Thubiani H H AbulreeshI M AlHazza and F Aqil ldquoLeaf extracts of Mangifera indicaL inhibit quorum sensing - Regulated production of virulencefactors and biofilm in test bacteriardquo Frontiers in Microbiologyvol 8 p 727 2017

[46] D G Renter J G Morris J M Sargeant et al ldquoPreva-lence risk factors O serogroups and virulence profiles ofshiga toxinndashproducing bacteria from cattle production environ-mentsrdquo Journal of Food Protection vol 68 no 8 pp 1556ndash15652005

[47] A R Hauser ldquoPseudomonas aeruginosa So many virulencefactors so little timerdquo Critical Care Medicine vol 39 no 9 pp2193-2194 2011

[48] R Le Berre S Nguyen E Nowak et al ldquoRelative contributionof three main virulence factors in Pseudomonas aeruginosapneumoniardquo Critical Care Medicine vol 39 no 9 pp 2113ndash2120 2011

[49] M M Gallardo-Garcia G Sanchez-Espin R Ivanova-Georgieva et al ldquoRelationship between pathogenic clinicaland virulence factors of Staphylococcus aureus in infectiveendocarditis versus uncomplicated bacteremia a case-controlstudyrdquo European Journal of Clinical Microbiology amp InfectiousDiseases vol 35 no 5 pp 821ndash828 2016

[50] F Sabouni S Mahmoudi A Bahador et al ldquoVirulence factorsof staphylococcus aureus isolates in an iranian referral childrenrsquoshospitalrdquo Osong Public Health and Research Perspectives vol 5no 2 pp 96ndash100 2014

[51] H M Aboushleib H M Omar R Abozahra A Elsheredyand K Baraka ldquoCorrelation of quorum sensing and virulencefactors in Pseudomonas aeruginosa isolates in Egyptrdquo TheJournal of Infection in Developing Countries vol 9 no 10 pp1091ndash1099 2015

[52] R T Sturbelle L F Avila T B Roos et al ldquoThe role ofquorum sensing in Escherichia coli (ETEC) virulence factorsrdquoVeterinary Microbiology vol 180 no 3-4 pp 245ndash252 2015

[53] J E Paczkowski S Mukherjee A R McCready et alldquoFlavonoids suppress Pseudomonas aeruginosa Virulencethrough allosteric inhibition of quorum-sensing receptorsrdquoTheJournal of Biological Chemistry vol 292 no 10 pp 4064ndash40762017

[54] L Weng Y Yang Y Zhang and L Wang ldquoA new syntheticligand that activatesQscRand blocks antibiotic-tolerant biofilmformation in Pseudomonas aeruginosardquo Applied Microbiologyand Biotechnology vol 98 no 6 pp 2565ndash2572 2014

[55] Y-X Yang Z-H Xu Y-Q Zhang J Tian L-X Wengand L-H Wang ldquoA new quorum-sensing inhibitor attenuatesvirulence and decreases antibiotic resistance in Pseudomonasaeruginosardquo Journal of Microbiology vol 50 no 6 pp 987ndash9932012

[56] J N Capilato S V Philippi T Reardon et al ldquoDevelopment ofa novel series of non-natural triaryl agonists and antagonists ofthe Pseudomonas aeruginosa LasR quorum sensing receptorrdquoBioorganic amp Medicinal Chemistry vol 25 no 1 pp 153ndash1652017

[57] C T OrsquoLoughlin L C Miller A Siryaporn K Drescher MF Semmelhack and B L Bassler ldquoA quorum-sensing inhibitorblocks Pseudomonas aeruginosa virulence and biofilm forma-tionrdquo Proceedings of the National Acadamy of Sciences of theUnited States of America vol 110 no 44 pp 17981ndash17986 2013

[58] G D Geske J C OrsquoNeill D M Miller M E Mattmannand H E Blackwell ldquoModulation of bacterial quorum sensingwith synthetic ligands systematic evaluation of N-acylatedhomoserine lactones in multiple species and new insights intotheir mechanisms of actionrdquo Journal of the American ChemicalSociety vol 129 no 44 pp 13613ndash13625 2007

[59] B K Khajanchi M L Kirtley S M Brackman A KChopra and B A McCormick ldquoImmunomodulatory and pro-tective roles of quorum-sensing signaling molecules N-acylhomoserine lactones during infection of mice with aeromonashydrophilardquo Infection and Immunity vol 79 no 7 pp 2646ndash2657 2011

[60] H Tomioka C Sano and Y Tatano ldquoHost-directed therapeu-tics against mycobacterial infectionsrdquo Current PharmaceuticalDesign vol 23 no 18 pp 2644ndash2656 2017

[61] M R Parsek D L Val B L Hanzelka J E Cronan Jr and EP Greenberg ldquoAcyl homoserine-lactone quorum-sensing signalgenerationrdquo Proceedings of the National Acadamy of Sciences ofthe United States of America vol 96 no 8 pp 4360ndash4365 1999

[62] MK Yadav SW Park SW Chae and J J Song ldquoSinefungin anatural nucleoside analogue of S-adenosylmethionine inhibitsStreptococcus pneumoniae biofilm growthrdquo BioMed ResearchInternational vol 2014 Article ID 156987 10 pages 2014

[63] M Hentzer and M Givskov ldquoPharmacological inhibition ofquorum sensing for the treatment of chronic bacterial infec-tionsrdquo The Journal of Clinical Investigation vol 112 no 9 pp1300ndash1307 2003

[64] V Singh G B Evans D H Lenz et al ldquoFemtomolar tran-sition state analogue inhibitors of 5rsquo-methylthioadenosineS-adenosylhomocysteine nucleosidase fromEscherichia colirdquoTheJournal of Biological Chemistry vol 280 no 18 pp 18265ndash182732005

[65] A Priyadarshi E E Kim and K Y Hwang ldquo Structuralinsights into Staphylococcus aureus enoyl-ACP reductase (FabI)

BioMed Research International 13

in complex with NADP and triclosan rdquo Proteins StructureFunction and Bioinformatics vol 78 no 2 pp 480ndash486 2010

[66] N Surolia and A Surolia ldquoTriclosan offers protection againstblood stages of malaria by inhibiting enoyl-ACP reductase ofPlasmodium falciparumrdquoNatureMedicine vol 7 no 2 pp 167ndash173 2001

[67] E Krol and A Becker ldquoRhizobial homologs of the fattyacid transporter FadL facilitate perception of long-chainacyl-homoserine lactone signalsrdquo Proceedings of the NationalAcadamy of Sciences of the United States of America vol 111 no29 pp 10702ndash10707 2014

[68] J L Copitch R N Whitehead and M A Webber ldquoPrevalenceof decreased susceptibility to triclosan in Salmonella entericaisolates fromanimals andhumans andassociationwithmultipledrug resistancerdquo International Journal of Antimicrobial Agentsvol 36 no 3 pp 247ndash251 2010

[69] S Lu N Wang S Ma X Hu L Kang and Y Yu ldquoParabensand triclosan in shellfish fromShenzhen coastal waters bioindi-cation of pollution and human health risksrdquo EnvironmentalPollution vol 246 pp 257ndash263 2018

[70] N Huma P Shankar J Kushwah et al ldquoDiversity and poly-morphism in AHL-Lactonase gene (aiiA) of Bacillusrdquo Journalof Microbiology and Biotechnology vol 21 no 10 pp 1001ndash10112011

[71] S Y Park B J Hwang M Shin J Kim H Kim and J LeeldquoN-acylhomoserine lactonase-producingRhodococcussppwithdifferent AHL-degrading activitiesrdquo FEMSMicrobiology Lettersvol 261 no 1 pp 102ndash108 2006

[72] A Guendouze L Plener J Bzdrenga et al ldquoEffect of quo-rum quenching lactonase in clinical isolates of pseudomonasaeruginosa and comparison with quorum sensing inhibitorsrdquoFrontiers in Microbiology vol 8 p 227 2017

[73] S Hraiech J Hiblot J Lafleur et al ldquoInhaled lactonase reducespseudomonas aeruginosa quorum sensing and mortality in ratpneumoniardquo PLoS ONE vol 9 no 10 Article ID e107125 2014

[74] J Y Chow Y Yang S B Tay K L Chua and W S YewldquoDisruption of biofilm formation by the human pathogenacinetobacter baumannii using engineered quorum-quenchinglactonasesrdquoAntimicrobial Agents andChemotherapy vol 58 no3 pp 1802ndash1805 2014

[75] X FanM Liang L Wang R Chen H Li and X Liu ldquoAii810 anovel cold-adapted N-acylhomoserine lactonase discovered inametagenome can strongly attenuate Pseudomonas aeruginosavirulence factors and biofilm formationrdquo Frontiers in Microbiol-ogy vol 8 p 1950 2017

[76] MM Sakr KM AboshanabW F ElkhatibMA Yassien andN AHassouna ldquoOverexpressed recombinant quorumquench-ing lactonase reduces the virulence motility and biofilm for-mationofmultidrug-resistant Pseudomonas aeruginosa clinicalisolatesrdquo Appl Microbiol Biotechnol vol 102 no 24 pp 10613ndash10622 2018

[77] C Schipper C Hornung P Bijtenhoorn M Quitschau SGrond andW R Streit ldquoMetagenome-derived clones encodingtwo novel lactonase family proteins involved in biofilm inhibi-tion in pseudomonas aeruginosardquo Applied and EnvironmentalMicrobiology vol 75 no 1 pp 224ndash233 2008

[78] W Dong J Zhu X Guo et al ldquoCharacterization of AiiKan AHL lactonase from Kurthia huakui LAM0618T and itsapplication in quorum quenching on Pseudomonas aeruginosaPAO1rdquo Scientific Reports vol 8 no 1 p 6013 2018

[79] W Liu C Ran Z Liu et al ldquoEffects of dietary Lactobacillusplantarum and AHL lactonase on the control of Aeromonas

hydrophila infection in tilapiardquoMicrobiologyopen vol 5 no 4pp 687ndash699 2016

[80] M Torres J C Reina J C Fuentes-Monteverde et al ldquoAHL-lactonase expression in three marine emerging pathogenicVibrio spp reduces virulence and mortality in brine shrimp(Artemia salina) and Manila clam (Venerupis philippinarum)rdquoPLoS ONE vol 13 no 4 Article ID e0195176 2018

[81] G Vinoj B Vaseeharan S Thomas A J Spiers and S ShanthildquoQuorum-quenching activity of the AHL-lactonase from bacil-lus licheniformis DAHB1 inhibits vibrio biofilm formation invitro and reduces shrimp intestinal colonisation andmortalityrdquoMarine Biotechnology vol 16 no 6 pp 707ndash715 2014

[82] V C Kalia ldquoIn search of versatile organisms for quorum-sensing inhibitors acyl homoserine lactones (AHL)-acylaseand AHL-lactonaserdquo FEMS Microbiology Letters vol 359 no2 p 143 2014

[83] V B Maisuria and A S Nerurkar ldquoInterference of quorumsensing by Delftia sp VM4 depends on the activity of a noveln-acylhomoserine lactone-acylaserdquo PLoS ONE vol 10 no 9Article ID e0138034 2015

[84] R Mukherji N K Varshney P Panigrahi C Suresh and APrabhune ldquoA new role for penicillin acylases degradation ofacyl homoserine lactone quorum sensing signals by Kluyveracitrophila penicillin G acylaserdquo Enzyme and Microbial Technol-ogy vol 56 pp 1ndash7 2014

[85] C F Sio L G Otten R H Cool et al ldquoQuorum quenchingby an N-acyl-homoserine lactone acylase from Pseudomonasaeruginosa PAO1rdquo Infection and Immunity vol 74 no 3 pp1673ndash1682 2006

[86] K Ivanova M M Fernandes E Mendoza and T TzanovldquoEnzyme multilayer coatings inhibit Pseudomonas aeruginosabiofilm formation on urinary cathetersrdquo Applied Microbiologyand Biotechnology vol 99 no 10 pp 4373ndash4385 2015

[87] N Grover J G Plaks S R Summers G R Chado M J Schurrand J L Kaar ldquoAcylase-containing polyurethane coatings withanti-biofilm activityrdquo Biotechnology and Bioengineering vol 113no 12 pp 2535ndash2543 2016

[88] J Lee I Lee J Nam D S Hwang K-M Yeon and JKim ldquoImmobilization and stabilization of acylase on carboxy-lated polyaniline nanofibers for highly effective antifoulingapplication via quorum quenchingrdquo ACS Applied Materials ampInterfaces vol 9 no 18 pp 15424ndash15432 2017

[89] S Uroz S R Chhabra M Camara P Williams P Ogerand Y Dessaux ldquoN-acylhomoserine lactone quorum-sensingmolecules are modified and degraded by Rhodococcus ery-thropolis W2 by both amidolytic and novel oxidoreductaseactivitiesrdquoMicrobiology vol 151 no 10 pp 3313ndash3322 2005

[90] B Eva and S Maria ldquoMicrobial secondary metabolites asinhibitors of pharmaceutically important transferases and oxi-doreductasesrdquo Ceska Slov Farm vol 61 no 3 pp 107ndash114 2012

[91] P Bijtenhoorn H Mayerhofer J Muller-Dieckmann et alldquoA novel metagenomic Short-Chain dehydrogenasereductaseattenuates pseudomonas Aeruginosa biofilm formation andvirulence on Caenorhabditis elegansrdquo PLoS ONE vol 6 no 10Article ID e26278 2011

[92] J D Wildschut R M Lang J K Voordouw and G Voor-douw ldquoRubredoxin oxygen oxidoreductase enhances survivalof desulfovibrio vulgaris hildenborough under microaerophilicconditionsrdquo Journal of Bacteriology vol 188 no 17 pp 6253ndash6260 2006

14 BioMed Research International

[93] X Zhang S Ou-yang JWang L Liao RWu and JWei ldquoCon-struction of antibacterial surface via layer-by-layer methodrdquoCurrent Pharmaceutical Design vol 24 no 8 pp 926ndash935 2018

[94] C Pustelny A Albers K Buldt-Karentzopoulos et al ldquoDiox-ygenase-mediated quenching of quinolone-dependent quorumsensing in pseudomonas aeruginosardquoChemistry amp Biology vol16 no 12 pp 1259ndash1267 2009

[95] J T Hodgkinson W R Galloway M Welch and DR Spring ldquoMicrowave-assisted preparation of the quorum-sensing molecule 2-heptyl-3-hydroxy-4(1H)-quinolone andstructurally related analogsrdquo Nature Protocols vol 7 no 6 pp1184ndash1192 2012

[96] F Witzgall T Depke M Hoffmann et al ldquoThe alkylquinolonerepertoire of Pseudomonas aeruginosa is linked to structuralflexibility of the fabh-like 2-heptyl-3-hydroxy-4(1H)-quinolone(PQS) biosynthesis enzyme PqsBCrdquo ChemBioChem vol 19 no14 pp 1531ndash1544 2018

[97] L Andresen E Sala V Koiv and A Mae ldquoA role for theRcs phosphorelay in regulating expression of plant cell walldegrading enzymes in Pectobacterium carotovorum subspcarotovorumrdquoMicrobiology vol 156 no 5 pp 1323ndash1334 2010

[98] L Andresen V Koiv T Alamae and A Mae ldquoThe Rcs phos-phorelay modulates the expression of plant cell wall degradingenzymes and virulence in Pectobacterium carotovorum sspcarotovorumrdquo FEMS Microbiology Letters vol 273 no 2 pp229ndash238 2007

[99] R K Gupta S Chhibber and K Harjai ldquoAcyl homoserinelactones from culture supernatants of pseudomonas aeruginosaaccelerate host immunomodulationrdquo PLoS ONE vol 6 no 6Article ID e20860 2011

[100] G F Kaufmann J Park J M Mee R J Ulevitch and KD Janda ldquoThe quorum quenching antibody RS2-1G9 protectsmacrophages from the cytotoxic effects of the Pseudomonasaeruginosa quorum sensing signalling molecule N-3-oxo-dodecanoyl-homoserine lactonerdquo Molecular Immunology vol45 no 9 pp 2710ndash2714 2008

[101] S Koul J Prakash A Mishra and V C Kalia ldquoPotential emer-gence of multi-quorum sensing inhibitor resistant (MQSIR)bacteriardquo Indian Journal of Microbiology vol 56 no 1 pp 1ndash182016

[102] T Praneenararat A G Palmer and H E Blackwell ldquoChemicalmethods to interrogate bacterial quorum sensing pathwaysrdquoOrganicampBiomolecular Chemistry vol 10 no 41 pp 8189ndash81992012

[103] J Park R Jagasia G F Kaufmann et al ldquoInfection controlby antibody disruption of bacterial quorum sensing signalingrdquoChemistry amp Biology vol 14 no 10 pp 1119ndash1127 2007

[104] C Grandclement M Tannieres S Morera Y Dessaux DFaure andM Camara ldquoQuorum quenching role in nature andapplied developmentsrdquo FEMSMicrobiology Reviews vol 40 no1 pp 86ndash116 2016

[105] MHan J GuG F Gao andW J Liu ldquoChina in action nationalstrategies to combat against emerging infectious diseasesrdquoScience China Life Sciences vol 60 no 12 pp 1383ndash1385 2017

[106] J Liu H Yu Y Huang et al ldquoComplete genome sequence ofa novel bacteriophage infecting Bradyrhizobium diazoefficiensUSDA110rdquo Science China Life Sciences vol 61 no 1 pp 118ndash1212018

[107] L D Christensen M van Gennip T H Jakobsen et alldquoSynergistic antibacterial efficacy of early combination treat-ment with tobramycin and quorum-sensing inhibitors against

Pseudomonas aeruginosa in an intraperitoneal foreign-bodyinfection mouse modelrdquo Journal of Antimicrobial Chemother-apy vol 67 no 5 pp 1198ndash1206 2012

[108] J Fong M Yuan T H Jakobsen et al ldquoDisulfide bond-containing ajoene analogues as novel quorum sensinginhibitors of Pseudomonas aeruginosardquo Journal of MedicinalChemistry vol 60 no 1 pp 215ndash227 2017

[109] R Garcıa-Contreras M Martınez-Vazquez N VelazquezGuadarrama et al ldquo Resistance to the quorum-quenchingcompounds brominated furanone C-30 and 5-fluorouracil inPseudomonas aeruginosa clinical isolates rdquo Pathogens and Dis-ease vol 68 no 1 pp 8ndash11 2013

[110] T H Jakobsen S K Bragason R K Phipps et al ldquoFood as asource for quorum sensing inhibitors iberin from horseradishrevealed as a quorum sensing inhibitor of pseudomonas aerug-inosardquo Applied and Environmental Microbiology vol 78 no 7pp 2410ndash2421 2012

[111] A Vadekeetil H Saini S Chhibber and K Harjai ldquo Exploitingthe antivirulence efficacy of an ajoene-ciprofloxacin combina-tion against Pseudomonas aeruginosa biofilm associatedmurineacute pyelonephritis rdquo Biofouling vol 32 no 4 pp 371ndash3822016

[112] S Bahari H Zeighami H Mirshahabi S Roudashti and FHaghi ldquoInhibition of pseudomonas aeruginosa quorum sensingby subinhibitory concentrations of curcumin with gentamicinand azithromycinrdquo Journal of Global Antimicrobial Resistancevol 10 pp 21ndash28 2017

[113] A S Roccaro A R Blanco F Giuliano D Rusciano and VEnea ldquoEpigallocatechin-gallate enhances the activity of tetra-cycline in staphylococci by inhibiting its efflux from bacterialcellsrdquo Antimicrobial Agents and Chemotherapy vol 48 no 6pp 1968ndash1973 2004

[114] C Chu J Deng Y Man and Y Qu ldquoGreen tea extractsepigallocatechin-3-gallate for different treatmentsrdquo BioMedResearch International vol 2017 Article ID 5615647 9 pages2017

[115] A Furiga B Lajoie S El Hage G Baziard and C RoquesldquoImpairment of pseudomonas aeruginosa biofilm resistance toantibiotics by combining the drugs with a new quorum-sensinginhibitorrdquo Antimicrobial Agents and Chemotherapy vol 60 no3 pp 1676ndash1686 2016

[116] Y Inoue N Togashi and H Hamashima ldquoFarnesol-induceddisruption of the staphylococcus aureus cytoplasmic mem-branerdquo Biological and Pharmaceutical Bulletin vol 39 no 5 pp653ndash656 2016

[117] C Kim D Hesek M Lee and S Mobashery ldquoPotentiationof the activity of beta-lactam antibiotics by farnesol and itsderivativesrdquo Bioorganic amp Medicinal Chemistry Letters vol 28no 4 pp 642ndash645 2018

[118] G Brackman P Cos L Maes H J Nelis and T Coenye ldquoQuo-rum sensing inhibitors increase the susceptibility of bacterialbiofilms to antibiotics in vitro and in vivordquoAntimicrobial Agentsand Chemotherapy vol 55 no 6 pp 2655ndash2661 2011

[119] G Brackman K Breyne R De Rycke et al ldquoThe quorum sens-ing inhibitor hamamelitannin increases antibiotic susceptibilityof staphylococcus aureus biofilms by affecting peptidoglycanbiosynthesis and eDNA releaserdquo Scientific Reports vol 6 ArticleID 20321 2016

[120] J M Walz R L Avelar K J Longtine K L Carter L A Mer-mel and S O Heard ldquoAnti-infective external coating of centralvenous catheters A randomized noninferiority trial comparing

BioMed Research International 15

5-fluorouracil with chlorhexidinesilver sulfadiazine in pre-venting catheter colonizationrdquo Critical Care Medicine vol 38no 11 pp 2095ndash2102 2010

[121] C van Delden T Kohler F Brunner-Ferber B Francois JCarlet and J Pechere ldquoAzithromycin to prevent Pseudomonasaeruginosa ventilator-associated pneumonia by inhibition ofquorum sensing a randomized controlled trialrdquo Intensive CareMedicine vol 38 no 7 pp 1118ndash1125 2012

[122] A R Smyth P M Cifelli C A Ortori et al ldquoGarlic asan inhibitor of Pseudomonas aeruginosa quorum sensing incystic fibrosisndasha pilot randomized controlled trialrdquo PediatricPulmonology vol 45 no 4 pp 356ndash362 2010

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Submit your manuscripts atwwwhindawicom

8 BioMed Research International

Table5Stud

iesd

emon

stratingQSdisrup

tionby

antib

odiestargetin

g

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

In-vitroandRA

W2647cells

Pseudomonas

aerugin

osa

Antibod

yRS2-1G9

generatedagainsta

3-oxo-do

decano

ylho

moserinelactone

analog

hapten

Targetingtheb

acteria

lN-3-oxo-dod

ecanoyl

homoserinelactone

molecules

Protectm

urineb

onem

arrow-derived

macroph

ages

from

thec

ytotoxiceffectsandalso

preventedthe

activ

ationof

them

itogen-activ

ated

proteinkinase

p38

[100]

In-vitro

Pseudomonas

aerugin

osa

Antibod

yXYD

-11G

2Hydrolyzing

N-3-(oxod

odecanoyl)-L-ho

moserine

lacton

eSupp

ressed

QSsig

nalin

g[101]

In-vitroandmou

semod

elStaphylococcus

aureus

Antibod

yAP4

-24H

11elicitedagainsta

ratio

nally

desig

nedhapten

Sequ

estrationof

thea

utoind

ucingp

eptid

e-4

Supp

ressed

Saureus

pathogenicity

inan

abscess

form

ationmou

semod

elin

vivo

andprovided

completep

rotectionagainsta

lethalStaphylococcus

aureus

challenge

[103]

BioMed Research International 9

Table6Stud

iesd

emon

stratingthes

ynergistice

ffectso

fanti-Q

Sagentsandantib

iotic

s

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

Mice

Pseudomonas

aerugin

osa

Furano

neC-

30ajoeneo

rho

rseradish

juicee

xtractin

Com

binatio

ncurcum

in

QSinhibitio

nenhancethe

sensitivity

ofpathogen

toantib

iotic

sRe

sultedin

anincreasedclearanceo

fPseud

omonas

aerugin

osain

aforeign

-bod

yinfectionmod

el

[107]

In-vitro

Pseudomonas

aerugin

osa

with

tobram

ycin

gentam

icin

and

azith

romycin

Indu

cedconcentrations

ofC1

2-ho

moserine

lacton

eand

C4-h

omoserinelactone

Curcum

inshow

edsynergisticeffectswith

azith

romycin

andgentam

icinC

ombinatio

nuse

redu

cedQS-relatedvirulencefactors

Dow

nregulated

QS-relatedgenes

[112]

In-vitro

Staphylococci

Epigallocatechin-3-gallate

with

Tetracyclin

eInhibitio

nof

thea

ctivity

ofTet(K

)pum

pseffl

uxpu

mps

ofad

ifferentclassTet(B

)En

hanced

theb

acteric

idaleffecto

fTetracyclineo

nStaphylococci

[113]

In-vitro

Pseudomonas

aerugin

osa

N-(2-pyrim

idyl)

butanamideC1

1Dow

nregulationof

rhlrhlA

andlasB

genes

Increasedthes

usceptibilityto

antib

iotic

sand

attenu

ated

thep

atho

genicityof

theb

acteriu

m

[115]

In-vitro

Staphylococcus

aureus

(methicillin-resistant

Sau

reus)

Farnesolwith120573-la

ctam

antib

iotic

s

Inhibitio

nof

lipasea

ctivity

anddisrup

tionof

thec

ytop

lasm

icmem

branethrou

ghthe

leakageo

fpotassiu

mions

Attenu

ated

ther

ateo

fgrowth

ofbacteriaand

coun

terin

gub

iquitous120573-la

ctam

resistancein

bacteria

[116117]

In-vitro

Cele

gansG

aller

iamellonellamice

Burkholderia

cenocepacia

Staphylococcus

aureus

Escherich

iacoli

Baicalin

hydrate

cinn

amaldehyde

hamam

elitann

inwith

Tobram

ycinvancomycin

andclindamycin

Inhibitio

nof

biofi

lmform

ation

QSinhibitio

nenhancethe

sensitivity

ofpathogen

toantib

iotic

s

Com

bining

theu

seof

antib

odyandanti-QSagents

increasedsusceptib

ilityof

theb

acteria

tothe

antib

iotic

and

increasedho

stsurvivalrateaft

erinfection

[118]

10 BioMed Research International

al found in their study [100] that the antibody RS2-1G9can bind to 3-oxo-C12-HSL in the extracellular environmentof Pseudomonas aeruginosa thereby attenuating the inflam-matory response of the host XYD-11G2 antibody has beenshown to catalyze the hydrolysis of 3-oxo-C12-HSL signalingthus inhibiting the pyocyanin production by Gram-negativebacteria [101 102] The monoclonal antibody AP4-24H11 wasfound to block the QS signal of Gram-positive Staphylococcusaureus by interfering with AIP IV [103] Another in vivo studyshowed that the antibody AP4-24H11 could significantlyattenuate the tissue necrosis in the infected model [104]Although these monoclonal antibodies have been identifiedto block the QS signaling of pathogenic bacteria (Table 5)their applications for treating bacterial diseases are still in theinitial stage

45 Combinations of Anti-QS Agents and Antibiotics Com-bining use of antibiotic with an anti-QS agent is the mosteffective clinical strategy for the treatment of bacterial dis-eases at present [105 106] Many studies have confirmed thesynergistic effect of antibiotics and anti-QS agents (Table 6)Ajoene furanone c-30 and horseradish extract have beenrevealed to reduce the expression of virulence factors inPseudomonas aeruginosa and make Pseudomonas aeruginosaeasier to be cleared by tobramycin [107ndash111] Another studyhas confirmed the synergistic effects of curcumin gentam-icin and azithromycin on Pseudomonas aeruginosa that isthe expressions of virulence genes were significantly down-regulated by the combining use of curcumin together withgentamicin or azithromycin and the therapeutic doses ofgentamicin and azithromycin were minimized by curcuminsupplementation [112] The anti-QS compounds such asgallocatechin 3-gallate and caffeic acid enhanced therapeuticeffects on Mycoplasma pneumoniae infection by combininguse with tetracycline ciprofloxacin or gentamicin [113 114]N-(2-pyrimidyl) butylamine was confirmed to enhance theantibacterial effect of tobramycin colistin and ciprofloxacinon Pseudomonas aeruginosa [115] Recent studies [116 117]have shown that both farnesol and hamamelitannin canreduce the virulence of Staphylococcus aureus and increasethe sensitivity of Staphylococcus aureus to 120573-lactam antibi-otics Synergistic effects of hamamelitannin baicalin hydratecinnamaldehyde and antibiotics have been demonstrated indifferent infection models [118 119]These findings imply thatcombining use of antibiotics with ant-QS agents has greattherapeutic potential for bacterial diseases

5 Conclusions

Regulating bacterial QS signaling by QS-targeted agents isan effective strategy to control the production of bacte-rial virulence factors and the formation of biofilm Thisnovel nonantibiotic therapy can inhibit the expression ofpathogenic genes prevent infection and reduce the riskof drug resistance of bacterial cells and has been widelyexploited in recent years A large number of studies haveidentified many anti-QS agents to control the pathogenicphenotypes ofmost bacteria and to attenuate the pathological

damage in various animal infection models However mostanti-QS agents are still in the preclinical phase and morehuman clinical trials are warranted to test their practicalfeasibility The results of several existing clinical studies [120ndash122] on anti-QS agents show that compared with antibioticsthe anti-QS compounds may have potential toxicity andtheir therapeutic effect is not as stable as that of antibioticswhich limited their extensive application Combining use ofanti-QS agents with conventional antibiotics can significantlyimprove the efficacy of therapeutic drugs and decrease thecost of human healthcare and is likely to be the mainapplication method of anti-QS agents for bacterial diseasestreatment in the future

Conflicts of Interest

The authors declare that there are no conflicts of interestregarding the publication of this paper

Acknowledgments

The authors are thankful to the China Scholarship Council(CSC) for both financial support and scholarships Theauthors appreciate Dr Ruiqiang Yang at the Nanjing Agri-culture University for his help on this review This workwas supported by the National Natural Science Foundationof China (31472107) the Youth Science Fund Project of theNational Natural Science Foundation of China (31702126)the Chinese Academy of Sciences lsquoHundred Talentrsquo awardthe National Science Foundation for Distinguished YoungScholars of Hunan Province (2016JJ1015) the Postgradu-ate Research and Innovation Project of Hunan Province(CX2017B348) the Hunan Province ldquoHunan Young Scienceand Technology Innovation Talentrdquo Project (2015RS4053)the Hunan Agricultural University Provincial Outstand-ing Doctoral Dissertation Cultivating Fund (YB2017002)and the Open Foundation of Key Laboratory of Agro-ecological Processes in Subtropical Region Institute ofSubtropical Agriculture Chinese Academy of Sciences(ISA2016101)

References

[1] M Etminan B Carleton J A C Delaney and R PadwalldquoAntibiotics ineffective for prevention of recurrentMIrdquo Journalof Family Practice vol 53 no 7 p 525 2004

[2] F E Akram T El-Tayeb K Abou-Aisha and M El-AzizildquoA combination of silver nanoparticles and visible blue lightenhances the antibacterial efficacy of ineffective antibioticsagainst methicillin-resistant Staphylococcus aureus (MRSA)rdquoAnnals of Clinical Microbiology and Antimicrobials vol 15 no1 p 48 2016

[3] L A Barton and M W Simon ldquoProphylactic antibioticsIneffective or inefficaciousrdquo Clinical Pediatrics vol 53 no 8 p813 2014

[4] J Neumaier ldquoAntibiotics are up to 90 ineffective what reallyhelps in common coldsrdquo MMWmdashFortschritte der Medizin vol153 no 3 pp 18-19 2011

BioMed Research International 11

[5] B Schlemmer ldquoBetter prescribing of antibiotics Preventing therisk of ineffective treatment in current infectionrdquo La Revue dupraticien vol 53 no 14 pp 1525-1526 2003

[6] P Stiefelhagen ldquoSuspected severe pneumonia Antibiotics areineffective - what nowrdquo MMWmdashFortschritte der Medizin vol157 no 17 p 28 2015

[7] Z Li and M Knetsch ldquoAntibacterial strategies for wounddressing preventing infection and stimulating healingrdquoCurrentPharmaceutical Design vol 24 no 8 pp 936ndash951 2018

[8] W Xu S Dong Y Han S Li and Y Liu ldquoHydrogels asantibacterial biomaterialsrdquo Current Pharmaceutical Design vol24 no 8 pp 843ndash854 2018

[9] ldquoMicrobiology by numbersrdquo Nature Reviews Microbiology vol9 no 9 p 628 2011

[10] J P Pearson E C Pesci and B H Iglewski ldquoRoles of Pseu-domonas aeruginosa las and rhl quorum-sensing systems incontrol of elastase and rhamnolipid biosynthesis genesrdquo Journalof Bacteriology vol 179 no 18 pp 5756ndash5767 1997

[11] C Van Delden E C Pesci J P Pearson and B H IglewskildquoStarvation selection restores elastase and rhamnolipid produc-tion in a Pseudomonas aeruginosa quorum-sensing mutantrdquoInfection and Immunity vol 66 no 9 pp 4499ndash4502 1998

[12] L E Dietrich A Price-Whelan A Petersen M Whiteley andD K Newman ldquoThe phenazine pyocyanin is a terminal sig-nalling factor in the quorum sensing network of Pseudomonasaeruginosardquo Molecular Microbiology vol 61 no 5 pp 1308ndash1321 2006

[13] E C Carnes D M Lopez N P Donegan et al ldquoConfinement-induced quorum sensing of individual Staphylococcus aureusbacteriardquoNature Chemical Biology vol 6 no 1 pp 41ndash45 2010

[14] J M Yarwood D J Bartels E M Volper and E P GreenbergldquoQuorum sensing in staphylococcus aureus biofilmsrdquo Journal ofBacteriology vol 186 no 6 pp 1838ndash1850 2004

[15] M J Eickhoff and B L Bassler ldquoSnapShot bacterial quorumsensingrdquo Cell vol 174 no 5 p 1328e1321 2018

[16] M Schuster D Joseph Sexton S P Diggle and E PeterGreenberg ldquoAcyl-homoserine lactone quorum sensing fromevolution to applicationrdquo Annual Review of Microbiology vol67 pp 43ndash63 2013

[17] MH SturmeMKleerebezem J NakayamaA D AkkermansE E Vaugha andWM DeVos ldquoCell to cell communication byautoinducing peptides in gram-positive bacteriardquo Antonie VanLeeuwenhoek vol 81 no 1ndash4 pp 233ndash243 2002

[18] C S Pereira J A Thompson and K B Xavier ldquoAI-2-mediatedsignalling in bacteriardquo FEMS Microbiology Reviews vol 37 no2 pp 156ndash181 2013

[19] M Yang K Sun L Zhou R Yang Z Zhong and J Zhu ldquoFunctional analysis of three AHL autoinducer synthase genes inMesorhizobium loti reveals the important role of quorum sens-ing in symbiotic nodulation rdquoCanadian Journal ofMicrobiologyvol 55 no 2 pp 210ndash214 2009

[20] A Ivanova K Ivanova and T Tzanov ldquoInhibition of Quorum-Sensing A New Paradigm in Controlling Bacterial Virulenceand Biofilm Formationrdquo in Biotechnological Applications ofQuorum Sensing Inhibitors V C Kalia Ed pp 5ndash10 2018

[21] Y Zeng Y Wang Z Yu and Y Huang ldquoHypersensitiveresponse of plasmid-encoded AHL synthase gene to lifestyleand nutrient by Ensifer adhaerens X097rdquo Frontiers in Microbiol-ogy vol 8 p 1160 2017

[22] A O Shpakov ldquoBacterial autoinducing peptidesrdquo Mikrobi-ologiia vol 78 no 3 pp 291ndash303 2009

[23] G J Lyon J S Wright T W Muir and R P Novick ldquoKeydeterminants of receptor activation in the agr autoinducingpeptides of Staphylococcus aureusrdquoBiochemistry vol 41 no 31pp 10095ndash10104 2002

[24] E J Murray and PWilliams ldquoDetection of agr-type autoinduc-ing peptides produced by staphylococcus aureusrdquo Methods inMolecular Biology vol 1673 pp 89ndash96 2018

[25] M J Martin S Clare D Goulding et al ldquoThe agr locus reg-ulates virulence and colonization genes in clostridium difficile027rdquo Journal of Bacteriology vol 195 no 16 pp 3672ndash3681 2013

[26] S Cheraghi L Pourgholi M Shafaati et al ldquoAnalysis ofvirulence genes and accessory gene regulator ( agr ) typesamong methicillin-resistant Staphylococcus aureus strains inIranrdquo Journal of Global Antimicrobial Resistance vol 10 pp 315ndash320 2017

[27] P Gilot G Lina T Cochard and B Poutrel ldquoAnalysis of thegenetic variability of genes encoding the RNA III-activatingcomponents Agr and TRAP in a population of Staphylococcusaureus strains isolated from cows with mastitisrdquo Journal ofClinical Microbiology vol 40 no 11 pp 4060ndash4067 2002

[28] G Lina S Jarraud G Ji et al ldquoTransmembrane topology andhistidine protein kinase activity of AgrC the agr signal receptorin Staphylococcus aureusrdquoMolecular Microbiology vol 28 no3 pp 655ndash662 1998

[29] M Guo S Gamby Y Zheng and H Sintim ldquoSmall moleculeinhibitors of AI-2 signaling in bacteria state-of-the-art andfuture perspectives for anti-quorum sensing agentsrdquo Interna-tional Journal of Molecular Sciences vol 14 no 9 pp 17694ndash17728 2013

[30] JThompson R Oliveira A Djukovic C Ubeda and K XavierldquoManipulation of the quorum sensing signal AI-2 affects theantibiotic-treated gut microbiotardquo Cell Reports vol 10 no 11pp 1861ndash1871 2015

[31] K R Hardie ldquoAutoinducer 2 activity in Escherichia coli culturesupernatants can be actively reduced despite maintenance of anactive synthase LuxSrdquoMicrobiology vol 149 no 3 pp 715ndash7282003

[32] J Wang F Li and Z Tian ldquoRole of microbiota on lunghomeostasis and diseasesrdquo Science China Life Sciences vol 60no 12 pp 1407ndash1415 2017

[33] K Riedel A Gotschlich M Givskov et al ldquoThe cep quorum-sensing system of Burkholderia cepacia H111 controls biofilmformation and swarming motilityrdquoMicrobiology vol 147 no 9pp 2517ndash2528 2001

[34] J C Linnes H Ma and J D Bryers ldquoGiant extracellular matrixbinding protein expression in staphylococcus epidermidis isregulated by biofilm formation and osmotic pressurerdquo CurrentMicrobiology vol 66 no 6 pp 627ndash633 2013

[35] AM Romanı K Fund J Artigas T Schwartz S Sabater andUObst ldquoRelevance of polymeric matrix enzymes during biofilmformationrdquoMicrobial Ecology vol 56 no 3 pp 427ndash436 2008

[36] I Kanwar A K Sah and P K Suresh ldquoBiofilm-mediatedantibiotic-resistant oral bacterial infections mechanism andcombat strategiesrdquo Current Pharmaceutical Design vol 23 no14 pp 2084ndash2095 2017

[37] S Keelara S Thakur and J Patel ldquoBiofilm formation byenvironmental isolates of Salmonella and their sensitivity tonatural antimicrobialsrdquo Foodborne Pathogens and Disease vol13 no 9 pp 509ndash516 2016

[38] F Sepandj H Ceri A Gibb R Read andMOlson ldquoMinimuminhibitory concentration versus minimum biofilm eliminating

12 BioMed Research International

concentration in evaluation of antibiotic sensitivity of entero-cocci causing peritonitisrdquo Peritoneal Dialysis International vol27 no 4 pp 464-465 2007

[39] B A Niemira and E B Solomon ldquoSensitivity of planktonicand biofilm-associated salmonella spp to ionizing radiationrdquoApplied andEnvironmentalMicrobiology vol 71 no 5 pp 2732ndash2736 2005

[40] A M Gamage G Shui M R Wenk and K L Chua ldquoN-Octanoylhomoserine lactone signalling mediated by the BpsI-BpsR quorum sensing system plays a major role in biofilmformationofBurkholderia pseudomalleirdquoMicrobiology vol 157no 4 pp 1176ndash1186 2011

[41] S H Hong M Hegde J Kim X Wang A Jayaraman andT K Wood ldquoSynthetic quorum-sensing circuit to controlconsortial biofilm formation and dispersal in a microfluidicdevicerdquo Nature Communications vol 3 p 613 2012

[42] P Sankar Ganesh and V Ravishankar Rai ldquoAttenuation ofquorum-sensing-dependent virulence factors and biofilm for-mation by medicinal plants against antibiotic resistant Pseu-domonas aeruginosardquo Journal of Traditional and Complemen-tary Medicine vol 8 no 1 pp 170ndash177 2018

[43] P Shih ldquoEffects of quorum-sensing deficiency on Pseudomonasaeruginosa biofilm formation and antibiotic resistancerdquo Journalof Antimicrobial Chemotherapy vol 49 no 2 pp 309ndash314

[44] M I Chernukha I A Shaginian IM Romanova G VMaleevand A L Gintsburg ldquoThe role of ldquoquorum sensingrdquo regula-tion system in symbiotic interaction of bacteria Burkholderiacepacia and Pseudomonas aeruginosa during mixed infectionrdquoZhurnalMikrobiologii Epidemiologii Immunobiologii no 4 pp32ndash37 2006

[45] F M Husain I Ahmad A S Al-Thubiani H H AbulreeshI M AlHazza and F Aqil ldquoLeaf extracts of Mangifera indicaL inhibit quorum sensing - Regulated production of virulencefactors and biofilm in test bacteriardquo Frontiers in Microbiologyvol 8 p 727 2017

[46] D G Renter J G Morris J M Sargeant et al ldquoPreva-lence risk factors O serogroups and virulence profiles ofshiga toxinndashproducing bacteria from cattle production environ-mentsrdquo Journal of Food Protection vol 68 no 8 pp 1556ndash15652005

[47] A R Hauser ldquoPseudomonas aeruginosa So many virulencefactors so little timerdquo Critical Care Medicine vol 39 no 9 pp2193-2194 2011

[48] R Le Berre S Nguyen E Nowak et al ldquoRelative contributionof three main virulence factors in Pseudomonas aeruginosapneumoniardquo Critical Care Medicine vol 39 no 9 pp 2113ndash2120 2011

[49] M M Gallardo-Garcia G Sanchez-Espin R Ivanova-Georgieva et al ldquoRelationship between pathogenic clinicaland virulence factors of Staphylococcus aureus in infectiveendocarditis versus uncomplicated bacteremia a case-controlstudyrdquo European Journal of Clinical Microbiology amp InfectiousDiseases vol 35 no 5 pp 821ndash828 2016

[50] F Sabouni S Mahmoudi A Bahador et al ldquoVirulence factorsof staphylococcus aureus isolates in an iranian referral childrenrsquoshospitalrdquo Osong Public Health and Research Perspectives vol 5no 2 pp 96ndash100 2014

[51] H M Aboushleib H M Omar R Abozahra A Elsheredyand K Baraka ldquoCorrelation of quorum sensing and virulencefactors in Pseudomonas aeruginosa isolates in Egyptrdquo TheJournal of Infection in Developing Countries vol 9 no 10 pp1091ndash1099 2015

[52] R T Sturbelle L F Avila T B Roos et al ldquoThe role ofquorum sensing in Escherichia coli (ETEC) virulence factorsrdquoVeterinary Microbiology vol 180 no 3-4 pp 245ndash252 2015

[53] J E Paczkowski S Mukherjee A R McCready et alldquoFlavonoids suppress Pseudomonas aeruginosa Virulencethrough allosteric inhibition of quorum-sensing receptorsrdquoTheJournal of Biological Chemistry vol 292 no 10 pp 4064ndash40762017

[54] L Weng Y Yang Y Zhang and L Wang ldquoA new syntheticligand that activatesQscRand blocks antibiotic-tolerant biofilmformation in Pseudomonas aeruginosardquo Applied Microbiologyand Biotechnology vol 98 no 6 pp 2565ndash2572 2014

[55] Y-X Yang Z-H Xu Y-Q Zhang J Tian L-X Wengand L-H Wang ldquoA new quorum-sensing inhibitor attenuatesvirulence and decreases antibiotic resistance in Pseudomonasaeruginosardquo Journal of Microbiology vol 50 no 6 pp 987ndash9932012

[56] J N Capilato S V Philippi T Reardon et al ldquoDevelopment ofa novel series of non-natural triaryl agonists and antagonists ofthe Pseudomonas aeruginosa LasR quorum sensing receptorrdquoBioorganic amp Medicinal Chemistry vol 25 no 1 pp 153ndash1652017

[57] C T OrsquoLoughlin L C Miller A Siryaporn K Drescher MF Semmelhack and B L Bassler ldquoA quorum-sensing inhibitorblocks Pseudomonas aeruginosa virulence and biofilm forma-tionrdquo Proceedings of the National Acadamy of Sciences of theUnited States of America vol 110 no 44 pp 17981ndash17986 2013

[58] G D Geske J C OrsquoNeill D M Miller M E Mattmannand H E Blackwell ldquoModulation of bacterial quorum sensingwith synthetic ligands systematic evaluation of N-acylatedhomoserine lactones in multiple species and new insights intotheir mechanisms of actionrdquo Journal of the American ChemicalSociety vol 129 no 44 pp 13613ndash13625 2007

[59] B K Khajanchi M L Kirtley S M Brackman A KChopra and B A McCormick ldquoImmunomodulatory and pro-tective roles of quorum-sensing signaling molecules N-acylhomoserine lactones during infection of mice with aeromonashydrophilardquo Infection and Immunity vol 79 no 7 pp 2646ndash2657 2011

[60] H Tomioka C Sano and Y Tatano ldquoHost-directed therapeu-tics against mycobacterial infectionsrdquo Current PharmaceuticalDesign vol 23 no 18 pp 2644ndash2656 2017

[61] M R Parsek D L Val B L Hanzelka J E Cronan Jr and EP Greenberg ldquoAcyl homoserine-lactone quorum-sensing signalgenerationrdquo Proceedings of the National Acadamy of Sciences ofthe United States of America vol 96 no 8 pp 4360ndash4365 1999

[62] MK Yadav SW Park SW Chae and J J Song ldquoSinefungin anatural nucleoside analogue of S-adenosylmethionine inhibitsStreptococcus pneumoniae biofilm growthrdquo BioMed ResearchInternational vol 2014 Article ID 156987 10 pages 2014

[63] M Hentzer and M Givskov ldquoPharmacological inhibition ofquorum sensing for the treatment of chronic bacterial infec-tionsrdquo The Journal of Clinical Investigation vol 112 no 9 pp1300ndash1307 2003

[64] V Singh G B Evans D H Lenz et al ldquoFemtomolar tran-sition state analogue inhibitors of 5rsquo-methylthioadenosineS-adenosylhomocysteine nucleosidase fromEscherichia colirdquoTheJournal of Biological Chemistry vol 280 no 18 pp 18265ndash182732005

[65] A Priyadarshi E E Kim and K Y Hwang ldquo Structuralinsights into Staphylococcus aureus enoyl-ACP reductase (FabI)

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in complex with NADP and triclosan rdquo Proteins StructureFunction and Bioinformatics vol 78 no 2 pp 480ndash486 2010

[66] N Surolia and A Surolia ldquoTriclosan offers protection againstblood stages of malaria by inhibiting enoyl-ACP reductase ofPlasmodium falciparumrdquoNatureMedicine vol 7 no 2 pp 167ndash173 2001

[67] E Krol and A Becker ldquoRhizobial homologs of the fattyacid transporter FadL facilitate perception of long-chainacyl-homoserine lactone signalsrdquo Proceedings of the NationalAcadamy of Sciences of the United States of America vol 111 no29 pp 10702ndash10707 2014

[68] J L Copitch R N Whitehead and M A Webber ldquoPrevalenceof decreased susceptibility to triclosan in Salmonella entericaisolates fromanimals andhumans andassociationwithmultipledrug resistancerdquo International Journal of Antimicrobial Agentsvol 36 no 3 pp 247ndash251 2010

[69] S Lu N Wang S Ma X Hu L Kang and Y Yu ldquoParabensand triclosan in shellfish fromShenzhen coastal waters bioindi-cation of pollution and human health risksrdquo EnvironmentalPollution vol 246 pp 257ndash263 2018

[70] N Huma P Shankar J Kushwah et al ldquoDiversity and poly-morphism in AHL-Lactonase gene (aiiA) of Bacillusrdquo Journalof Microbiology and Biotechnology vol 21 no 10 pp 1001ndash10112011

[71] S Y Park B J Hwang M Shin J Kim H Kim and J LeeldquoN-acylhomoserine lactonase-producingRhodococcussppwithdifferent AHL-degrading activitiesrdquo FEMSMicrobiology Lettersvol 261 no 1 pp 102ndash108 2006

[72] A Guendouze L Plener J Bzdrenga et al ldquoEffect of quo-rum quenching lactonase in clinical isolates of pseudomonasaeruginosa and comparison with quorum sensing inhibitorsrdquoFrontiers in Microbiology vol 8 p 227 2017

[73] S Hraiech J Hiblot J Lafleur et al ldquoInhaled lactonase reducespseudomonas aeruginosa quorum sensing and mortality in ratpneumoniardquo PLoS ONE vol 9 no 10 Article ID e107125 2014

[74] J Y Chow Y Yang S B Tay K L Chua and W S YewldquoDisruption of biofilm formation by the human pathogenacinetobacter baumannii using engineered quorum-quenchinglactonasesrdquoAntimicrobial Agents andChemotherapy vol 58 no3 pp 1802ndash1805 2014

[75] X FanM Liang L Wang R Chen H Li and X Liu ldquoAii810 anovel cold-adapted N-acylhomoserine lactonase discovered inametagenome can strongly attenuate Pseudomonas aeruginosavirulence factors and biofilm formationrdquo Frontiers in Microbiol-ogy vol 8 p 1950 2017

[76] MM Sakr KM AboshanabW F ElkhatibMA Yassien andN AHassouna ldquoOverexpressed recombinant quorumquench-ing lactonase reduces the virulence motility and biofilm for-mationofmultidrug-resistant Pseudomonas aeruginosa clinicalisolatesrdquo Appl Microbiol Biotechnol vol 102 no 24 pp 10613ndash10622 2018

[77] C Schipper C Hornung P Bijtenhoorn M Quitschau SGrond andW R Streit ldquoMetagenome-derived clones encodingtwo novel lactonase family proteins involved in biofilm inhibi-tion in pseudomonas aeruginosardquo Applied and EnvironmentalMicrobiology vol 75 no 1 pp 224ndash233 2008

[78] W Dong J Zhu X Guo et al ldquoCharacterization of AiiKan AHL lactonase from Kurthia huakui LAM0618T and itsapplication in quorum quenching on Pseudomonas aeruginosaPAO1rdquo Scientific Reports vol 8 no 1 p 6013 2018

[79] W Liu C Ran Z Liu et al ldquoEffects of dietary Lactobacillusplantarum and AHL lactonase on the control of Aeromonas

hydrophila infection in tilapiardquoMicrobiologyopen vol 5 no 4pp 687ndash699 2016

[80] M Torres J C Reina J C Fuentes-Monteverde et al ldquoAHL-lactonase expression in three marine emerging pathogenicVibrio spp reduces virulence and mortality in brine shrimp(Artemia salina) and Manila clam (Venerupis philippinarum)rdquoPLoS ONE vol 13 no 4 Article ID e0195176 2018

[81] G Vinoj B Vaseeharan S Thomas A J Spiers and S ShanthildquoQuorum-quenching activity of the AHL-lactonase from bacil-lus licheniformis DAHB1 inhibits vibrio biofilm formation invitro and reduces shrimp intestinal colonisation andmortalityrdquoMarine Biotechnology vol 16 no 6 pp 707ndash715 2014

[82] V C Kalia ldquoIn search of versatile organisms for quorum-sensing inhibitors acyl homoserine lactones (AHL)-acylaseand AHL-lactonaserdquo FEMS Microbiology Letters vol 359 no2 p 143 2014

[83] V B Maisuria and A S Nerurkar ldquoInterference of quorumsensing by Delftia sp VM4 depends on the activity of a noveln-acylhomoserine lactone-acylaserdquo PLoS ONE vol 10 no 9Article ID e0138034 2015

[84] R Mukherji N K Varshney P Panigrahi C Suresh and APrabhune ldquoA new role for penicillin acylases degradation ofacyl homoserine lactone quorum sensing signals by Kluyveracitrophila penicillin G acylaserdquo Enzyme and Microbial Technol-ogy vol 56 pp 1ndash7 2014

[85] C F Sio L G Otten R H Cool et al ldquoQuorum quenchingby an N-acyl-homoserine lactone acylase from Pseudomonasaeruginosa PAO1rdquo Infection and Immunity vol 74 no 3 pp1673ndash1682 2006

[86] K Ivanova M M Fernandes E Mendoza and T TzanovldquoEnzyme multilayer coatings inhibit Pseudomonas aeruginosabiofilm formation on urinary cathetersrdquo Applied Microbiologyand Biotechnology vol 99 no 10 pp 4373ndash4385 2015

[87] N Grover J G Plaks S R Summers G R Chado M J Schurrand J L Kaar ldquoAcylase-containing polyurethane coatings withanti-biofilm activityrdquo Biotechnology and Bioengineering vol 113no 12 pp 2535ndash2543 2016

[88] J Lee I Lee J Nam D S Hwang K-M Yeon and JKim ldquoImmobilization and stabilization of acylase on carboxy-lated polyaniline nanofibers for highly effective antifoulingapplication via quorum quenchingrdquo ACS Applied Materials ampInterfaces vol 9 no 18 pp 15424ndash15432 2017

[89] S Uroz S R Chhabra M Camara P Williams P Ogerand Y Dessaux ldquoN-acylhomoserine lactone quorum-sensingmolecules are modified and degraded by Rhodococcus ery-thropolis W2 by both amidolytic and novel oxidoreductaseactivitiesrdquoMicrobiology vol 151 no 10 pp 3313ndash3322 2005

[90] B Eva and S Maria ldquoMicrobial secondary metabolites asinhibitors of pharmaceutically important transferases and oxi-doreductasesrdquo Ceska Slov Farm vol 61 no 3 pp 107ndash114 2012

[91] P Bijtenhoorn H Mayerhofer J Muller-Dieckmann et alldquoA novel metagenomic Short-Chain dehydrogenasereductaseattenuates pseudomonas Aeruginosa biofilm formation andvirulence on Caenorhabditis elegansrdquo PLoS ONE vol 6 no 10Article ID e26278 2011

[92] J D Wildschut R M Lang J K Voordouw and G Voor-douw ldquoRubredoxin oxygen oxidoreductase enhances survivalof desulfovibrio vulgaris hildenborough under microaerophilicconditionsrdquo Journal of Bacteriology vol 188 no 17 pp 6253ndash6260 2006

14 BioMed Research International

[93] X Zhang S Ou-yang JWang L Liao RWu and JWei ldquoCon-struction of antibacterial surface via layer-by-layer methodrdquoCurrent Pharmaceutical Design vol 24 no 8 pp 926ndash935 2018

[94] C Pustelny A Albers K Buldt-Karentzopoulos et al ldquoDiox-ygenase-mediated quenching of quinolone-dependent quorumsensing in pseudomonas aeruginosardquoChemistry amp Biology vol16 no 12 pp 1259ndash1267 2009

[95] J T Hodgkinson W R Galloway M Welch and DR Spring ldquoMicrowave-assisted preparation of the quorum-sensing molecule 2-heptyl-3-hydroxy-4(1H)-quinolone andstructurally related analogsrdquo Nature Protocols vol 7 no 6 pp1184ndash1192 2012

[96] F Witzgall T Depke M Hoffmann et al ldquoThe alkylquinolonerepertoire of Pseudomonas aeruginosa is linked to structuralflexibility of the fabh-like 2-heptyl-3-hydroxy-4(1H)-quinolone(PQS) biosynthesis enzyme PqsBCrdquo ChemBioChem vol 19 no14 pp 1531ndash1544 2018

[97] L Andresen E Sala V Koiv and A Mae ldquoA role for theRcs phosphorelay in regulating expression of plant cell walldegrading enzymes in Pectobacterium carotovorum subspcarotovorumrdquoMicrobiology vol 156 no 5 pp 1323ndash1334 2010

[98] L Andresen V Koiv T Alamae and A Mae ldquoThe Rcs phos-phorelay modulates the expression of plant cell wall degradingenzymes and virulence in Pectobacterium carotovorum sspcarotovorumrdquo FEMS Microbiology Letters vol 273 no 2 pp229ndash238 2007

[99] R K Gupta S Chhibber and K Harjai ldquoAcyl homoserinelactones from culture supernatants of pseudomonas aeruginosaaccelerate host immunomodulationrdquo PLoS ONE vol 6 no 6Article ID e20860 2011

[100] G F Kaufmann J Park J M Mee R J Ulevitch and KD Janda ldquoThe quorum quenching antibody RS2-1G9 protectsmacrophages from the cytotoxic effects of the Pseudomonasaeruginosa quorum sensing signalling molecule N-3-oxo-dodecanoyl-homoserine lactonerdquo Molecular Immunology vol45 no 9 pp 2710ndash2714 2008

[101] S Koul J Prakash A Mishra and V C Kalia ldquoPotential emer-gence of multi-quorum sensing inhibitor resistant (MQSIR)bacteriardquo Indian Journal of Microbiology vol 56 no 1 pp 1ndash182016

[102] T Praneenararat A G Palmer and H E Blackwell ldquoChemicalmethods to interrogate bacterial quorum sensing pathwaysrdquoOrganicampBiomolecular Chemistry vol 10 no 41 pp 8189ndash81992012

[103] J Park R Jagasia G F Kaufmann et al ldquoInfection controlby antibody disruption of bacterial quorum sensing signalingrdquoChemistry amp Biology vol 14 no 10 pp 1119ndash1127 2007

[104] C Grandclement M Tannieres S Morera Y Dessaux DFaure andM Camara ldquoQuorum quenching role in nature andapplied developmentsrdquo FEMSMicrobiology Reviews vol 40 no1 pp 86ndash116 2016

[105] MHan J GuG F Gao andW J Liu ldquoChina in action nationalstrategies to combat against emerging infectious diseasesrdquoScience China Life Sciences vol 60 no 12 pp 1383ndash1385 2017

[106] J Liu H Yu Y Huang et al ldquoComplete genome sequence ofa novel bacteriophage infecting Bradyrhizobium diazoefficiensUSDA110rdquo Science China Life Sciences vol 61 no 1 pp 118ndash1212018

[107] L D Christensen M van Gennip T H Jakobsen et alldquoSynergistic antibacterial efficacy of early combination treat-ment with tobramycin and quorum-sensing inhibitors against

Pseudomonas aeruginosa in an intraperitoneal foreign-bodyinfection mouse modelrdquo Journal of Antimicrobial Chemother-apy vol 67 no 5 pp 1198ndash1206 2012

[108] J Fong M Yuan T H Jakobsen et al ldquoDisulfide bond-containing ajoene analogues as novel quorum sensinginhibitors of Pseudomonas aeruginosardquo Journal of MedicinalChemistry vol 60 no 1 pp 215ndash227 2017

[109] R Garcıa-Contreras M Martınez-Vazquez N VelazquezGuadarrama et al ldquo Resistance to the quorum-quenchingcompounds brominated furanone C-30 and 5-fluorouracil inPseudomonas aeruginosa clinical isolates rdquo Pathogens and Dis-ease vol 68 no 1 pp 8ndash11 2013

[110] T H Jakobsen S K Bragason R K Phipps et al ldquoFood as asource for quorum sensing inhibitors iberin from horseradishrevealed as a quorum sensing inhibitor of pseudomonas aerug-inosardquo Applied and Environmental Microbiology vol 78 no 7pp 2410ndash2421 2012

[111] A Vadekeetil H Saini S Chhibber and K Harjai ldquo Exploitingthe antivirulence efficacy of an ajoene-ciprofloxacin combina-tion against Pseudomonas aeruginosa biofilm associatedmurineacute pyelonephritis rdquo Biofouling vol 32 no 4 pp 371ndash3822016

[112] S Bahari H Zeighami H Mirshahabi S Roudashti and FHaghi ldquoInhibition of pseudomonas aeruginosa quorum sensingby subinhibitory concentrations of curcumin with gentamicinand azithromycinrdquo Journal of Global Antimicrobial Resistancevol 10 pp 21ndash28 2017

[113] A S Roccaro A R Blanco F Giuliano D Rusciano and VEnea ldquoEpigallocatechin-gallate enhances the activity of tetra-cycline in staphylococci by inhibiting its efflux from bacterialcellsrdquo Antimicrobial Agents and Chemotherapy vol 48 no 6pp 1968ndash1973 2004

[114] C Chu J Deng Y Man and Y Qu ldquoGreen tea extractsepigallocatechin-3-gallate for different treatmentsrdquo BioMedResearch International vol 2017 Article ID 5615647 9 pages2017

[115] A Furiga B Lajoie S El Hage G Baziard and C RoquesldquoImpairment of pseudomonas aeruginosa biofilm resistance toantibiotics by combining the drugs with a new quorum-sensinginhibitorrdquo Antimicrobial Agents and Chemotherapy vol 60 no3 pp 1676ndash1686 2016

[116] Y Inoue N Togashi and H Hamashima ldquoFarnesol-induceddisruption of the staphylococcus aureus cytoplasmic mem-branerdquo Biological and Pharmaceutical Bulletin vol 39 no 5 pp653ndash656 2016

[117] C Kim D Hesek M Lee and S Mobashery ldquoPotentiationof the activity of beta-lactam antibiotics by farnesol and itsderivativesrdquo Bioorganic amp Medicinal Chemistry Letters vol 28no 4 pp 642ndash645 2018

[118] G Brackman P Cos L Maes H J Nelis and T Coenye ldquoQuo-rum sensing inhibitors increase the susceptibility of bacterialbiofilms to antibiotics in vitro and in vivordquoAntimicrobial Agentsand Chemotherapy vol 55 no 6 pp 2655ndash2661 2011

[119] G Brackman K Breyne R De Rycke et al ldquoThe quorum sens-ing inhibitor hamamelitannin increases antibiotic susceptibilityof staphylococcus aureus biofilms by affecting peptidoglycanbiosynthesis and eDNA releaserdquo Scientific Reports vol 6 ArticleID 20321 2016

[120] J M Walz R L Avelar K J Longtine K L Carter L A Mer-mel and S O Heard ldquoAnti-infective external coating of centralvenous catheters A randomized noninferiority trial comparing

BioMed Research International 15

5-fluorouracil with chlorhexidinesilver sulfadiazine in pre-venting catheter colonizationrdquo Critical Care Medicine vol 38no 11 pp 2095ndash2102 2010

[121] C van Delden T Kohler F Brunner-Ferber B Francois JCarlet and J Pechere ldquoAzithromycin to prevent Pseudomonasaeruginosa ventilator-associated pneumonia by inhibition ofquorum sensing a randomized controlled trialrdquo Intensive CareMedicine vol 38 no 7 pp 1118ndash1125 2012

[122] A R Smyth P M Cifelli C A Ortori et al ldquoGarlic asan inhibitor of Pseudomonas aeruginosa quorum sensing incystic fibrosisndasha pilot randomized controlled trialrdquo PediatricPulmonology vol 45 no 4 pp 356ndash362 2010

Hindawiwwwhindawicom

International Journal of

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Anatomy Research International

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The Scientific World Journal

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Hindawiwwwhindawicom Volume 2018

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Hindawiwwwhindawicom Volume 2018

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Hindawiwwwhindawicom Volume 2018

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ArchaeaHindawiwwwhindawicom Volume 2018

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Nucleic AcidsJournal of

Volume 2018

Submit your manuscripts atwwwhindawicom

BioMed Research International 9

Table6Stud

iesd

emon

stratingthes

ynergistice

ffectso

fanti-Q

Sagentsandantib

iotic

s

Mod

els

Strains

Anti-Q

Sagents

Target

Effects

Ref

Mice

Pseudomonas

aerugin

osa

Furano

neC-

30ajoeneo

rho

rseradish

juicee

xtractin

Com

binatio

ncurcum

in

QSinhibitio

nenhancethe

sensitivity

ofpathogen

toantib

iotic

sRe

sultedin

anincreasedclearanceo

fPseud

omonas

aerugin

osain

aforeign

-bod

yinfectionmod

el

[107]

In-vitro

Pseudomonas

aerugin

osa

with

tobram

ycin

gentam

icin

and

azith

romycin

Indu

cedconcentrations

ofC1

2-ho

moserine

lacton

eand

C4-h

omoserinelactone

Curcum

inshow

edsynergisticeffectswith

azith

romycin

andgentam

icinC

ombinatio

nuse

redu

cedQS-relatedvirulencefactors

Dow

nregulated

QS-relatedgenes

[112]

In-vitro

Staphylococci

Epigallocatechin-3-gallate

with

Tetracyclin

eInhibitio

nof

thea

ctivity

ofTet(K

)pum

pseffl

uxpu

mps

ofad

ifferentclassTet(B

)En

hanced

theb

acteric

idaleffecto

fTetracyclineo

nStaphylococci

[113]

In-vitro

Pseudomonas

aerugin

osa

N-(2-pyrim

idyl)

butanamideC1

1Dow

nregulationof

rhlrhlA

andlasB

genes

Increasedthes

usceptibilityto

antib

iotic

sand

attenu

ated

thep

atho

genicityof

theb

acteriu

m

[115]

In-vitro

Staphylococcus

aureus

(methicillin-resistant

Sau

reus)

Farnesolwith120573-la

ctam

antib

iotic

s

Inhibitio

nof

lipasea

ctivity

anddisrup

tionof

thec

ytop

lasm

icmem

branethrou

ghthe

leakageo

fpotassiu

mions

Attenu

ated

ther

ateo

fgrowth

ofbacteriaand

coun

terin

gub

iquitous120573-la

ctam

resistancein

bacteria

[116117]

In-vitro

Cele

gansG

aller

iamellonellamice

Burkholderia

cenocepacia

Staphylococcus

aureus

Escherich

iacoli

Baicalin

hydrate

cinn

amaldehyde

hamam

elitann

inwith

Tobram

ycinvancomycin

andclindamycin

Inhibitio

nof

biofi

lmform

ation

QSinhibitio

nenhancethe

sensitivity

ofpathogen

toantib

iotic

s

Com

bining

theu

seof

antib

odyandanti-QSagents

increasedsusceptib

ilityof

theb

acteria

tothe

antib

iotic

and

increasedho

stsurvivalrateaft

erinfection

[118]

10 BioMed Research International

al found in their study [100] that the antibody RS2-1G9can bind to 3-oxo-C12-HSL in the extracellular environmentof Pseudomonas aeruginosa thereby attenuating the inflam-matory response of the host XYD-11G2 antibody has beenshown to catalyze the hydrolysis of 3-oxo-C12-HSL signalingthus inhibiting the pyocyanin production by Gram-negativebacteria [101 102] The monoclonal antibody AP4-24H11 wasfound to block the QS signal of Gram-positive Staphylococcusaureus by interfering with AIP IV [103] Another in vivo studyshowed that the antibody AP4-24H11 could significantlyattenuate the tissue necrosis in the infected model [104]Although these monoclonal antibodies have been identifiedto block the QS signaling of pathogenic bacteria (Table 5)their applications for treating bacterial diseases are still in theinitial stage

45 Combinations of Anti-QS Agents and Antibiotics Com-bining use of antibiotic with an anti-QS agent is the mosteffective clinical strategy for the treatment of bacterial dis-eases at present [105 106] Many studies have confirmed thesynergistic effect of antibiotics and anti-QS agents (Table 6)Ajoene furanone c-30 and horseradish extract have beenrevealed to reduce the expression of virulence factors inPseudomonas aeruginosa and make Pseudomonas aeruginosaeasier to be cleared by tobramycin [107ndash111] Another studyhas confirmed the synergistic effects of curcumin gentam-icin and azithromycin on Pseudomonas aeruginosa that isthe expressions of virulence genes were significantly down-regulated by the combining use of curcumin together withgentamicin or azithromycin and the therapeutic doses ofgentamicin and azithromycin were minimized by curcuminsupplementation [112] The anti-QS compounds such asgallocatechin 3-gallate and caffeic acid enhanced therapeuticeffects on Mycoplasma pneumoniae infection by combininguse with tetracycline ciprofloxacin or gentamicin [113 114]N-(2-pyrimidyl) butylamine was confirmed to enhance theantibacterial effect of tobramycin colistin and ciprofloxacinon Pseudomonas aeruginosa [115] Recent studies [116 117]have shown that both farnesol and hamamelitannin canreduce the virulence of Staphylococcus aureus and increasethe sensitivity of Staphylococcus aureus to 120573-lactam antibi-otics Synergistic effects of hamamelitannin baicalin hydratecinnamaldehyde and antibiotics have been demonstrated indifferent infection models [118 119]These findings imply thatcombining use of antibiotics with ant-QS agents has greattherapeutic potential for bacterial diseases

5 Conclusions

Regulating bacterial QS signaling by QS-targeted agents isan effective strategy to control the production of bacte-rial virulence factors and the formation of biofilm Thisnovel nonantibiotic therapy can inhibit the expression ofpathogenic genes prevent infection and reduce the riskof drug resistance of bacterial cells and has been widelyexploited in recent years A large number of studies haveidentified many anti-QS agents to control the pathogenicphenotypes ofmost bacteria and to attenuate the pathological

damage in various animal infection models However mostanti-QS agents are still in the preclinical phase and morehuman clinical trials are warranted to test their practicalfeasibility The results of several existing clinical studies [120ndash122] on anti-QS agents show that compared with antibioticsthe anti-QS compounds may have potential toxicity andtheir therapeutic effect is not as stable as that of antibioticswhich limited their extensive application Combining use ofanti-QS agents with conventional antibiotics can significantlyimprove the efficacy of therapeutic drugs and decrease thecost of human healthcare and is likely to be the mainapplication method of anti-QS agents for bacterial diseasestreatment in the future

Conflicts of Interest

The authors declare that there are no conflicts of interestregarding the publication of this paper

Acknowledgments

The authors are thankful to the China Scholarship Council(CSC) for both financial support and scholarships Theauthors appreciate Dr Ruiqiang Yang at the Nanjing Agri-culture University for his help on this review This workwas supported by the National Natural Science Foundationof China (31472107) the Youth Science Fund Project of theNational Natural Science Foundation of China (31702126)the Chinese Academy of Sciences lsquoHundred Talentrsquo awardthe National Science Foundation for Distinguished YoungScholars of Hunan Province (2016JJ1015) the Postgradu-ate Research and Innovation Project of Hunan Province(CX2017B348) the Hunan Province ldquoHunan Young Scienceand Technology Innovation Talentrdquo Project (2015RS4053)the Hunan Agricultural University Provincial Outstand-ing Doctoral Dissertation Cultivating Fund (YB2017002)and the Open Foundation of Key Laboratory of Agro-ecological Processes in Subtropical Region Institute ofSubtropical Agriculture Chinese Academy of Sciences(ISA2016101)

References

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[2] F E Akram T El-Tayeb K Abou-Aisha and M El-AzizildquoA combination of silver nanoparticles and visible blue lightenhances the antibacterial efficacy of ineffective antibioticsagainst methicillin-resistant Staphylococcus aureus (MRSA)rdquoAnnals of Clinical Microbiology and Antimicrobials vol 15 no1 p 48 2016

[3] L A Barton and M W Simon ldquoProphylactic antibioticsIneffective or inefficaciousrdquo Clinical Pediatrics vol 53 no 8 p813 2014

[4] J Neumaier ldquoAntibiotics are up to 90 ineffective what reallyhelps in common coldsrdquo MMWmdashFortschritte der Medizin vol153 no 3 pp 18-19 2011

BioMed Research International 11

[5] B Schlemmer ldquoBetter prescribing of antibiotics Preventing therisk of ineffective treatment in current infectionrdquo La Revue dupraticien vol 53 no 14 pp 1525-1526 2003

[6] P Stiefelhagen ldquoSuspected severe pneumonia Antibiotics areineffective - what nowrdquo MMWmdashFortschritte der Medizin vol157 no 17 p 28 2015

[7] Z Li and M Knetsch ldquoAntibacterial strategies for wounddressing preventing infection and stimulating healingrdquoCurrentPharmaceutical Design vol 24 no 8 pp 936ndash951 2018

[8] W Xu S Dong Y Han S Li and Y Liu ldquoHydrogels asantibacterial biomaterialsrdquo Current Pharmaceutical Design vol24 no 8 pp 843ndash854 2018

[9] ldquoMicrobiology by numbersrdquo Nature Reviews Microbiology vol9 no 9 p 628 2011

[10] J P Pearson E C Pesci and B H Iglewski ldquoRoles of Pseu-domonas aeruginosa las and rhl quorum-sensing systems incontrol of elastase and rhamnolipid biosynthesis genesrdquo Journalof Bacteriology vol 179 no 18 pp 5756ndash5767 1997

[11] C Van Delden E C Pesci J P Pearson and B H IglewskildquoStarvation selection restores elastase and rhamnolipid produc-tion in a Pseudomonas aeruginosa quorum-sensing mutantrdquoInfection and Immunity vol 66 no 9 pp 4499ndash4502 1998

[12] L E Dietrich A Price-Whelan A Petersen M Whiteley andD K Newman ldquoThe phenazine pyocyanin is a terminal sig-nalling factor in the quorum sensing network of Pseudomonasaeruginosardquo Molecular Microbiology vol 61 no 5 pp 1308ndash1321 2006

[13] E C Carnes D M Lopez N P Donegan et al ldquoConfinement-induced quorum sensing of individual Staphylococcus aureusbacteriardquoNature Chemical Biology vol 6 no 1 pp 41ndash45 2010

[14] J M Yarwood D J Bartels E M Volper and E P GreenbergldquoQuorum sensing in staphylococcus aureus biofilmsrdquo Journal ofBacteriology vol 186 no 6 pp 1838ndash1850 2004

[15] M J Eickhoff and B L Bassler ldquoSnapShot bacterial quorumsensingrdquo Cell vol 174 no 5 p 1328e1321 2018

[16] M Schuster D Joseph Sexton S P Diggle and E PeterGreenberg ldquoAcyl-homoserine lactone quorum sensing fromevolution to applicationrdquo Annual Review of Microbiology vol67 pp 43ndash63 2013

[17] MH SturmeMKleerebezem J NakayamaA D AkkermansE E Vaugha andWM DeVos ldquoCell to cell communication byautoinducing peptides in gram-positive bacteriardquo Antonie VanLeeuwenhoek vol 81 no 1ndash4 pp 233ndash243 2002

[18] C S Pereira J A Thompson and K B Xavier ldquoAI-2-mediatedsignalling in bacteriardquo FEMS Microbiology Reviews vol 37 no2 pp 156ndash181 2013

[19] M Yang K Sun L Zhou R Yang Z Zhong and J Zhu ldquoFunctional analysis of three AHL autoinducer synthase genes inMesorhizobium loti reveals the important role of quorum sens-ing in symbiotic nodulation rdquoCanadian Journal ofMicrobiologyvol 55 no 2 pp 210ndash214 2009

[20] A Ivanova K Ivanova and T Tzanov ldquoInhibition of Quorum-Sensing A New Paradigm in Controlling Bacterial Virulenceand Biofilm Formationrdquo in Biotechnological Applications ofQuorum Sensing Inhibitors V C Kalia Ed pp 5ndash10 2018

[21] Y Zeng Y Wang Z Yu and Y Huang ldquoHypersensitiveresponse of plasmid-encoded AHL synthase gene to lifestyleand nutrient by Ensifer adhaerens X097rdquo Frontiers in Microbiol-ogy vol 8 p 1160 2017

[22] A O Shpakov ldquoBacterial autoinducing peptidesrdquo Mikrobi-ologiia vol 78 no 3 pp 291ndash303 2009

[23] G J Lyon J S Wright T W Muir and R P Novick ldquoKeydeterminants of receptor activation in the agr autoinducingpeptides of Staphylococcus aureusrdquoBiochemistry vol 41 no 31pp 10095ndash10104 2002

[24] E J Murray and PWilliams ldquoDetection of agr-type autoinduc-ing peptides produced by staphylococcus aureusrdquo Methods inMolecular Biology vol 1673 pp 89ndash96 2018

[25] M J Martin S Clare D Goulding et al ldquoThe agr locus reg-ulates virulence and colonization genes in clostridium difficile027rdquo Journal of Bacteriology vol 195 no 16 pp 3672ndash3681 2013

[26] S Cheraghi L Pourgholi M Shafaati et al ldquoAnalysis ofvirulence genes and accessory gene regulator ( agr ) typesamong methicillin-resistant Staphylococcus aureus strains inIranrdquo Journal of Global Antimicrobial Resistance vol 10 pp 315ndash320 2017

[27] P Gilot G Lina T Cochard and B Poutrel ldquoAnalysis of thegenetic variability of genes encoding the RNA III-activatingcomponents Agr and TRAP in a population of Staphylococcusaureus strains isolated from cows with mastitisrdquo Journal ofClinical Microbiology vol 40 no 11 pp 4060ndash4067 2002

[28] G Lina S Jarraud G Ji et al ldquoTransmembrane topology andhistidine protein kinase activity of AgrC the agr signal receptorin Staphylococcus aureusrdquoMolecular Microbiology vol 28 no3 pp 655ndash662 1998

[29] M Guo S Gamby Y Zheng and H Sintim ldquoSmall moleculeinhibitors of AI-2 signaling in bacteria state-of-the-art andfuture perspectives for anti-quorum sensing agentsrdquo Interna-tional Journal of Molecular Sciences vol 14 no 9 pp 17694ndash17728 2013

[30] JThompson R Oliveira A Djukovic C Ubeda and K XavierldquoManipulation of the quorum sensing signal AI-2 affects theantibiotic-treated gut microbiotardquo Cell Reports vol 10 no 11pp 1861ndash1871 2015

[31] K R Hardie ldquoAutoinducer 2 activity in Escherichia coli culturesupernatants can be actively reduced despite maintenance of anactive synthase LuxSrdquoMicrobiology vol 149 no 3 pp 715ndash7282003

[32] J Wang F Li and Z Tian ldquoRole of microbiota on lunghomeostasis and diseasesrdquo Science China Life Sciences vol 60no 12 pp 1407ndash1415 2017

[33] K Riedel A Gotschlich M Givskov et al ldquoThe cep quorum-sensing system of Burkholderia cepacia H111 controls biofilmformation and swarming motilityrdquoMicrobiology vol 147 no 9pp 2517ndash2528 2001

[34] J C Linnes H Ma and J D Bryers ldquoGiant extracellular matrixbinding protein expression in staphylococcus epidermidis isregulated by biofilm formation and osmotic pressurerdquo CurrentMicrobiology vol 66 no 6 pp 627ndash633 2013

[35] AM Romanı K Fund J Artigas T Schwartz S Sabater andUObst ldquoRelevance of polymeric matrix enzymes during biofilmformationrdquoMicrobial Ecology vol 56 no 3 pp 427ndash436 2008

[36] I Kanwar A K Sah and P K Suresh ldquoBiofilm-mediatedantibiotic-resistant oral bacterial infections mechanism andcombat strategiesrdquo Current Pharmaceutical Design vol 23 no14 pp 2084ndash2095 2017

[37] S Keelara S Thakur and J Patel ldquoBiofilm formation byenvironmental isolates of Salmonella and their sensitivity tonatural antimicrobialsrdquo Foodborne Pathogens and Disease vol13 no 9 pp 509ndash516 2016

[38] F Sepandj H Ceri A Gibb R Read andMOlson ldquoMinimuminhibitory concentration versus minimum biofilm eliminating

12 BioMed Research International

concentration in evaluation of antibiotic sensitivity of entero-cocci causing peritonitisrdquo Peritoneal Dialysis International vol27 no 4 pp 464-465 2007

[39] B A Niemira and E B Solomon ldquoSensitivity of planktonicand biofilm-associated salmonella spp to ionizing radiationrdquoApplied andEnvironmentalMicrobiology vol 71 no 5 pp 2732ndash2736 2005

[40] A M Gamage G Shui M R Wenk and K L Chua ldquoN-Octanoylhomoserine lactone signalling mediated by the BpsI-BpsR quorum sensing system plays a major role in biofilmformationofBurkholderia pseudomalleirdquoMicrobiology vol 157no 4 pp 1176ndash1186 2011

[41] S H Hong M Hegde J Kim X Wang A Jayaraman andT K Wood ldquoSynthetic quorum-sensing circuit to controlconsortial biofilm formation and dispersal in a microfluidicdevicerdquo Nature Communications vol 3 p 613 2012

[42] P Sankar Ganesh and V Ravishankar Rai ldquoAttenuation ofquorum-sensing-dependent virulence factors and biofilm for-mation by medicinal plants against antibiotic resistant Pseu-domonas aeruginosardquo Journal of Traditional and Complemen-tary Medicine vol 8 no 1 pp 170ndash177 2018

[43] P Shih ldquoEffects of quorum-sensing deficiency on Pseudomonasaeruginosa biofilm formation and antibiotic resistancerdquo Journalof Antimicrobial Chemotherapy vol 49 no 2 pp 309ndash314

[44] M I Chernukha I A Shaginian IM Romanova G VMaleevand A L Gintsburg ldquoThe role of ldquoquorum sensingrdquo regula-tion system in symbiotic interaction of bacteria Burkholderiacepacia and Pseudomonas aeruginosa during mixed infectionrdquoZhurnalMikrobiologii Epidemiologii Immunobiologii no 4 pp32ndash37 2006

[45] F M Husain I Ahmad A S Al-Thubiani H H AbulreeshI M AlHazza and F Aqil ldquoLeaf extracts of Mangifera indicaL inhibit quorum sensing - Regulated production of virulencefactors and biofilm in test bacteriardquo Frontiers in Microbiologyvol 8 p 727 2017

[46] D G Renter J G Morris J M Sargeant et al ldquoPreva-lence risk factors O serogroups and virulence profiles ofshiga toxinndashproducing bacteria from cattle production environ-mentsrdquo Journal of Food Protection vol 68 no 8 pp 1556ndash15652005

[47] A R Hauser ldquoPseudomonas aeruginosa So many virulencefactors so little timerdquo Critical Care Medicine vol 39 no 9 pp2193-2194 2011

[48] R Le Berre S Nguyen E Nowak et al ldquoRelative contributionof three main virulence factors in Pseudomonas aeruginosapneumoniardquo Critical Care Medicine vol 39 no 9 pp 2113ndash2120 2011

[49] M M Gallardo-Garcia G Sanchez-Espin R Ivanova-Georgieva et al ldquoRelationship between pathogenic clinicaland virulence factors of Staphylococcus aureus in infectiveendocarditis versus uncomplicated bacteremia a case-controlstudyrdquo European Journal of Clinical Microbiology amp InfectiousDiseases vol 35 no 5 pp 821ndash828 2016

[50] F Sabouni S Mahmoudi A Bahador et al ldquoVirulence factorsof staphylococcus aureus isolates in an iranian referral childrenrsquoshospitalrdquo Osong Public Health and Research Perspectives vol 5no 2 pp 96ndash100 2014

[51] H M Aboushleib H M Omar R Abozahra A Elsheredyand K Baraka ldquoCorrelation of quorum sensing and virulencefactors in Pseudomonas aeruginosa isolates in Egyptrdquo TheJournal of Infection in Developing Countries vol 9 no 10 pp1091ndash1099 2015

[52] R T Sturbelle L F Avila T B Roos et al ldquoThe role ofquorum sensing in Escherichia coli (ETEC) virulence factorsrdquoVeterinary Microbiology vol 180 no 3-4 pp 245ndash252 2015

[53] J E Paczkowski S Mukherjee A R McCready et alldquoFlavonoids suppress Pseudomonas aeruginosa Virulencethrough allosteric inhibition of quorum-sensing receptorsrdquoTheJournal of Biological Chemistry vol 292 no 10 pp 4064ndash40762017

[54] L Weng Y Yang Y Zhang and L Wang ldquoA new syntheticligand that activatesQscRand blocks antibiotic-tolerant biofilmformation in Pseudomonas aeruginosardquo Applied Microbiologyand Biotechnology vol 98 no 6 pp 2565ndash2572 2014

[55] Y-X Yang Z-H Xu Y-Q Zhang J Tian L-X Wengand L-H Wang ldquoA new quorum-sensing inhibitor attenuatesvirulence and decreases antibiotic resistance in Pseudomonasaeruginosardquo Journal of Microbiology vol 50 no 6 pp 987ndash9932012

[56] J N Capilato S V Philippi T Reardon et al ldquoDevelopment ofa novel series of non-natural triaryl agonists and antagonists ofthe Pseudomonas aeruginosa LasR quorum sensing receptorrdquoBioorganic amp Medicinal Chemistry vol 25 no 1 pp 153ndash1652017

[57] C T OrsquoLoughlin L C Miller A Siryaporn K Drescher MF Semmelhack and B L Bassler ldquoA quorum-sensing inhibitorblocks Pseudomonas aeruginosa virulence and biofilm forma-tionrdquo Proceedings of the National Acadamy of Sciences of theUnited States of America vol 110 no 44 pp 17981ndash17986 2013

[58] G D Geske J C OrsquoNeill D M Miller M E Mattmannand H E Blackwell ldquoModulation of bacterial quorum sensingwith synthetic ligands systematic evaluation of N-acylatedhomoserine lactones in multiple species and new insights intotheir mechanisms of actionrdquo Journal of the American ChemicalSociety vol 129 no 44 pp 13613ndash13625 2007

[59] B K Khajanchi M L Kirtley S M Brackman A KChopra and B A McCormick ldquoImmunomodulatory and pro-tective roles of quorum-sensing signaling molecules N-acylhomoserine lactones during infection of mice with aeromonashydrophilardquo Infection and Immunity vol 79 no 7 pp 2646ndash2657 2011

[60] H Tomioka C Sano and Y Tatano ldquoHost-directed therapeu-tics against mycobacterial infectionsrdquo Current PharmaceuticalDesign vol 23 no 18 pp 2644ndash2656 2017

[61] M R Parsek D L Val B L Hanzelka J E Cronan Jr and EP Greenberg ldquoAcyl homoserine-lactone quorum-sensing signalgenerationrdquo Proceedings of the National Acadamy of Sciences ofthe United States of America vol 96 no 8 pp 4360ndash4365 1999

[62] MK Yadav SW Park SW Chae and J J Song ldquoSinefungin anatural nucleoside analogue of S-adenosylmethionine inhibitsStreptococcus pneumoniae biofilm growthrdquo BioMed ResearchInternational vol 2014 Article ID 156987 10 pages 2014

[63] M Hentzer and M Givskov ldquoPharmacological inhibition ofquorum sensing for the treatment of chronic bacterial infec-tionsrdquo The Journal of Clinical Investigation vol 112 no 9 pp1300ndash1307 2003

[64] V Singh G B Evans D H Lenz et al ldquoFemtomolar tran-sition state analogue inhibitors of 5rsquo-methylthioadenosineS-adenosylhomocysteine nucleosidase fromEscherichia colirdquoTheJournal of Biological Chemistry vol 280 no 18 pp 18265ndash182732005

[65] A Priyadarshi E E Kim and K Y Hwang ldquo Structuralinsights into Staphylococcus aureus enoyl-ACP reductase (FabI)

BioMed Research International 13

in complex with NADP and triclosan rdquo Proteins StructureFunction and Bioinformatics vol 78 no 2 pp 480ndash486 2010

[66] N Surolia and A Surolia ldquoTriclosan offers protection againstblood stages of malaria by inhibiting enoyl-ACP reductase ofPlasmodium falciparumrdquoNatureMedicine vol 7 no 2 pp 167ndash173 2001

[67] E Krol and A Becker ldquoRhizobial homologs of the fattyacid transporter FadL facilitate perception of long-chainacyl-homoserine lactone signalsrdquo Proceedings of the NationalAcadamy of Sciences of the United States of America vol 111 no29 pp 10702ndash10707 2014

[68] J L Copitch R N Whitehead and M A Webber ldquoPrevalenceof decreased susceptibility to triclosan in Salmonella entericaisolates fromanimals andhumans andassociationwithmultipledrug resistancerdquo International Journal of Antimicrobial Agentsvol 36 no 3 pp 247ndash251 2010

[69] S Lu N Wang S Ma X Hu L Kang and Y Yu ldquoParabensand triclosan in shellfish fromShenzhen coastal waters bioindi-cation of pollution and human health risksrdquo EnvironmentalPollution vol 246 pp 257ndash263 2018

[70] N Huma P Shankar J Kushwah et al ldquoDiversity and poly-morphism in AHL-Lactonase gene (aiiA) of Bacillusrdquo Journalof Microbiology and Biotechnology vol 21 no 10 pp 1001ndash10112011

[71] S Y Park B J Hwang M Shin J Kim H Kim and J LeeldquoN-acylhomoserine lactonase-producingRhodococcussppwithdifferent AHL-degrading activitiesrdquo FEMSMicrobiology Lettersvol 261 no 1 pp 102ndash108 2006

[72] A Guendouze L Plener J Bzdrenga et al ldquoEffect of quo-rum quenching lactonase in clinical isolates of pseudomonasaeruginosa and comparison with quorum sensing inhibitorsrdquoFrontiers in Microbiology vol 8 p 227 2017

[73] S Hraiech J Hiblot J Lafleur et al ldquoInhaled lactonase reducespseudomonas aeruginosa quorum sensing and mortality in ratpneumoniardquo PLoS ONE vol 9 no 10 Article ID e107125 2014

[74] J Y Chow Y Yang S B Tay K L Chua and W S YewldquoDisruption of biofilm formation by the human pathogenacinetobacter baumannii using engineered quorum-quenchinglactonasesrdquoAntimicrobial Agents andChemotherapy vol 58 no3 pp 1802ndash1805 2014

[75] X FanM Liang L Wang R Chen H Li and X Liu ldquoAii810 anovel cold-adapted N-acylhomoserine lactonase discovered inametagenome can strongly attenuate Pseudomonas aeruginosavirulence factors and biofilm formationrdquo Frontiers in Microbiol-ogy vol 8 p 1950 2017

[76] MM Sakr KM AboshanabW F ElkhatibMA Yassien andN AHassouna ldquoOverexpressed recombinant quorumquench-ing lactonase reduces the virulence motility and biofilm for-mationofmultidrug-resistant Pseudomonas aeruginosa clinicalisolatesrdquo Appl Microbiol Biotechnol vol 102 no 24 pp 10613ndash10622 2018

[77] C Schipper C Hornung P Bijtenhoorn M Quitschau SGrond andW R Streit ldquoMetagenome-derived clones encodingtwo novel lactonase family proteins involved in biofilm inhibi-tion in pseudomonas aeruginosardquo Applied and EnvironmentalMicrobiology vol 75 no 1 pp 224ndash233 2008

[78] W Dong J Zhu X Guo et al ldquoCharacterization of AiiKan AHL lactonase from Kurthia huakui LAM0618T and itsapplication in quorum quenching on Pseudomonas aeruginosaPAO1rdquo Scientific Reports vol 8 no 1 p 6013 2018

[79] W Liu C Ran Z Liu et al ldquoEffects of dietary Lactobacillusplantarum and AHL lactonase on the control of Aeromonas

hydrophila infection in tilapiardquoMicrobiologyopen vol 5 no 4pp 687ndash699 2016

[80] M Torres J C Reina J C Fuentes-Monteverde et al ldquoAHL-lactonase expression in three marine emerging pathogenicVibrio spp reduces virulence and mortality in brine shrimp(Artemia salina) and Manila clam (Venerupis philippinarum)rdquoPLoS ONE vol 13 no 4 Article ID e0195176 2018

[81] G Vinoj B Vaseeharan S Thomas A J Spiers and S ShanthildquoQuorum-quenching activity of the AHL-lactonase from bacil-lus licheniformis DAHB1 inhibits vibrio biofilm formation invitro and reduces shrimp intestinal colonisation andmortalityrdquoMarine Biotechnology vol 16 no 6 pp 707ndash715 2014

[82] V C Kalia ldquoIn search of versatile organisms for quorum-sensing inhibitors acyl homoserine lactones (AHL)-acylaseand AHL-lactonaserdquo FEMS Microbiology Letters vol 359 no2 p 143 2014

[83] V B Maisuria and A S Nerurkar ldquoInterference of quorumsensing by Delftia sp VM4 depends on the activity of a noveln-acylhomoserine lactone-acylaserdquo PLoS ONE vol 10 no 9Article ID e0138034 2015

[84] R Mukherji N K Varshney P Panigrahi C Suresh and APrabhune ldquoA new role for penicillin acylases degradation ofacyl homoserine lactone quorum sensing signals by Kluyveracitrophila penicillin G acylaserdquo Enzyme and Microbial Technol-ogy vol 56 pp 1ndash7 2014

[85] C F Sio L G Otten R H Cool et al ldquoQuorum quenchingby an N-acyl-homoserine lactone acylase from Pseudomonasaeruginosa PAO1rdquo Infection and Immunity vol 74 no 3 pp1673ndash1682 2006

[86] K Ivanova M M Fernandes E Mendoza and T TzanovldquoEnzyme multilayer coatings inhibit Pseudomonas aeruginosabiofilm formation on urinary cathetersrdquo Applied Microbiologyand Biotechnology vol 99 no 10 pp 4373ndash4385 2015

[87] N Grover J G Plaks S R Summers G R Chado M J Schurrand J L Kaar ldquoAcylase-containing polyurethane coatings withanti-biofilm activityrdquo Biotechnology and Bioengineering vol 113no 12 pp 2535ndash2543 2016

[88] J Lee I Lee J Nam D S Hwang K-M Yeon and JKim ldquoImmobilization and stabilization of acylase on carboxy-lated polyaniline nanofibers for highly effective antifoulingapplication via quorum quenchingrdquo ACS Applied Materials ampInterfaces vol 9 no 18 pp 15424ndash15432 2017

[89] S Uroz S R Chhabra M Camara P Williams P Ogerand Y Dessaux ldquoN-acylhomoserine lactone quorum-sensingmolecules are modified and degraded by Rhodococcus ery-thropolis W2 by both amidolytic and novel oxidoreductaseactivitiesrdquoMicrobiology vol 151 no 10 pp 3313ndash3322 2005

[90] B Eva and S Maria ldquoMicrobial secondary metabolites asinhibitors of pharmaceutically important transferases and oxi-doreductasesrdquo Ceska Slov Farm vol 61 no 3 pp 107ndash114 2012

[91] P Bijtenhoorn H Mayerhofer J Muller-Dieckmann et alldquoA novel metagenomic Short-Chain dehydrogenasereductaseattenuates pseudomonas Aeruginosa biofilm formation andvirulence on Caenorhabditis elegansrdquo PLoS ONE vol 6 no 10Article ID e26278 2011

[92] J D Wildschut R M Lang J K Voordouw and G Voor-douw ldquoRubredoxin oxygen oxidoreductase enhances survivalof desulfovibrio vulgaris hildenborough under microaerophilicconditionsrdquo Journal of Bacteriology vol 188 no 17 pp 6253ndash6260 2006

14 BioMed Research International

[93] X Zhang S Ou-yang JWang L Liao RWu and JWei ldquoCon-struction of antibacterial surface via layer-by-layer methodrdquoCurrent Pharmaceutical Design vol 24 no 8 pp 926ndash935 2018

[94] C Pustelny A Albers K Buldt-Karentzopoulos et al ldquoDiox-ygenase-mediated quenching of quinolone-dependent quorumsensing in pseudomonas aeruginosardquoChemistry amp Biology vol16 no 12 pp 1259ndash1267 2009

[95] J T Hodgkinson W R Galloway M Welch and DR Spring ldquoMicrowave-assisted preparation of the quorum-sensing molecule 2-heptyl-3-hydroxy-4(1H)-quinolone andstructurally related analogsrdquo Nature Protocols vol 7 no 6 pp1184ndash1192 2012

[96] F Witzgall T Depke M Hoffmann et al ldquoThe alkylquinolonerepertoire of Pseudomonas aeruginosa is linked to structuralflexibility of the fabh-like 2-heptyl-3-hydroxy-4(1H)-quinolone(PQS) biosynthesis enzyme PqsBCrdquo ChemBioChem vol 19 no14 pp 1531ndash1544 2018

[97] L Andresen E Sala V Koiv and A Mae ldquoA role for theRcs phosphorelay in regulating expression of plant cell walldegrading enzymes in Pectobacterium carotovorum subspcarotovorumrdquoMicrobiology vol 156 no 5 pp 1323ndash1334 2010

[98] L Andresen V Koiv T Alamae and A Mae ldquoThe Rcs phos-phorelay modulates the expression of plant cell wall degradingenzymes and virulence in Pectobacterium carotovorum sspcarotovorumrdquo FEMS Microbiology Letters vol 273 no 2 pp229ndash238 2007

[99] R K Gupta S Chhibber and K Harjai ldquoAcyl homoserinelactones from culture supernatants of pseudomonas aeruginosaaccelerate host immunomodulationrdquo PLoS ONE vol 6 no 6Article ID e20860 2011

[100] G F Kaufmann J Park J M Mee R J Ulevitch and KD Janda ldquoThe quorum quenching antibody RS2-1G9 protectsmacrophages from the cytotoxic effects of the Pseudomonasaeruginosa quorum sensing signalling molecule N-3-oxo-dodecanoyl-homoserine lactonerdquo Molecular Immunology vol45 no 9 pp 2710ndash2714 2008

[101] S Koul J Prakash A Mishra and V C Kalia ldquoPotential emer-gence of multi-quorum sensing inhibitor resistant (MQSIR)bacteriardquo Indian Journal of Microbiology vol 56 no 1 pp 1ndash182016

[102] T Praneenararat A G Palmer and H E Blackwell ldquoChemicalmethods to interrogate bacterial quorum sensing pathwaysrdquoOrganicampBiomolecular Chemistry vol 10 no 41 pp 8189ndash81992012

[103] J Park R Jagasia G F Kaufmann et al ldquoInfection controlby antibody disruption of bacterial quorum sensing signalingrdquoChemistry amp Biology vol 14 no 10 pp 1119ndash1127 2007

[104] C Grandclement M Tannieres S Morera Y Dessaux DFaure andM Camara ldquoQuorum quenching role in nature andapplied developmentsrdquo FEMSMicrobiology Reviews vol 40 no1 pp 86ndash116 2016

[105] MHan J GuG F Gao andW J Liu ldquoChina in action nationalstrategies to combat against emerging infectious diseasesrdquoScience China Life Sciences vol 60 no 12 pp 1383ndash1385 2017

[106] J Liu H Yu Y Huang et al ldquoComplete genome sequence ofa novel bacteriophage infecting Bradyrhizobium diazoefficiensUSDA110rdquo Science China Life Sciences vol 61 no 1 pp 118ndash1212018

[107] L D Christensen M van Gennip T H Jakobsen et alldquoSynergistic antibacterial efficacy of early combination treat-ment with tobramycin and quorum-sensing inhibitors against

Pseudomonas aeruginosa in an intraperitoneal foreign-bodyinfection mouse modelrdquo Journal of Antimicrobial Chemother-apy vol 67 no 5 pp 1198ndash1206 2012

[108] J Fong M Yuan T H Jakobsen et al ldquoDisulfide bond-containing ajoene analogues as novel quorum sensinginhibitors of Pseudomonas aeruginosardquo Journal of MedicinalChemistry vol 60 no 1 pp 215ndash227 2017

[109] R Garcıa-Contreras M Martınez-Vazquez N VelazquezGuadarrama et al ldquo Resistance to the quorum-quenchingcompounds brominated furanone C-30 and 5-fluorouracil inPseudomonas aeruginosa clinical isolates rdquo Pathogens and Dis-ease vol 68 no 1 pp 8ndash11 2013

[110] T H Jakobsen S K Bragason R K Phipps et al ldquoFood as asource for quorum sensing inhibitors iberin from horseradishrevealed as a quorum sensing inhibitor of pseudomonas aerug-inosardquo Applied and Environmental Microbiology vol 78 no 7pp 2410ndash2421 2012

[111] A Vadekeetil H Saini S Chhibber and K Harjai ldquo Exploitingthe antivirulence efficacy of an ajoene-ciprofloxacin combina-tion against Pseudomonas aeruginosa biofilm associatedmurineacute pyelonephritis rdquo Biofouling vol 32 no 4 pp 371ndash3822016

[112] S Bahari H Zeighami H Mirshahabi S Roudashti and FHaghi ldquoInhibition of pseudomonas aeruginosa quorum sensingby subinhibitory concentrations of curcumin with gentamicinand azithromycinrdquo Journal of Global Antimicrobial Resistancevol 10 pp 21ndash28 2017

[113] A S Roccaro A R Blanco F Giuliano D Rusciano and VEnea ldquoEpigallocatechin-gallate enhances the activity of tetra-cycline in staphylococci by inhibiting its efflux from bacterialcellsrdquo Antimicrobial Agents and Chemotherapy vol 48 no 6pp 1968ndash1973 2004

[114] C Chu J Deng Y Man and Y Qu ldquoGreen tea extractsepigallocatechin-3-gallate for different treatmentsrdquo BioMedResearch International vol 2017 Article ID 5615647 9 pages2017

[115] A Furiga B Lajoie S El Hage G Baziard and C RoquesldquoImpairment of pseudomonas aeruginosa biofilm resistance toantibiotics by combining the drugs with a new quorum-sensinginhibitorrdquo Antimicrobial Agents and Chemotherapy vol 60 no3 pp 1676ndash1686 2016

[116] Y Inoue N Togashi and H Hamashima ldquoFarnesol-induceddisruption of the staphylococcus aureus cytoplasmic mem-branerdquo Biological and Pharmaceutical Bulletin vol 39 no 5 pp653ndash656 2016

[117] C Kim D Hesek M Lee and S Mobashery ldquoPotentiationof the activity of beta-lactam antibiotics by farnesol and itsderivativesrdquo Bioorganic amp Medicinal Chemistry Letters vol 28no 4 pp 642ndash645 2018

[118] G Brackman P Cos L Maes H J Nelis and T Coenye ldquoQuo-rum sensing inhibitors increase the susceptibility of bacterialbiofilms to antibiotics in vitro and in vivordquoAntimicrobial Agentsand Chemotherapy vol 55 no 6 pp 2655ndash2661 2011

[119] G Brackman K Breyne R De Rycke et al ldquoThe quorum sens-ing inhibitor hamamelitannin increases antibiotic susceptibilityof staphylococcus aureus biofilms by affecting peptidoglycanbiosynthesis and eDNA releaserdquo Scientific Reports vol 6 ArticleID 20321 2016

[120] J M Walz R L Avelar K J Longtine K L Carter L A Mer-mel and S O Heard ldquoAnti-infective external coating of centralvenous catheters A randomized noninferiority trial comparing

BioMed Research International 15

5-fluorouracil with chlorhexidinesilver sulfadiazine in pre-venting catheter colonizationrdquo Critical Care Medicine vol 38no 11 pp 2095ndash2102 2010

[121] C van Delden T Kohler F Brunner-Ferber B Francois JCarlet and J Pechere ldquoAzithromycin to prevent Pseudomonasaeruginosa ventilator-associated pneumonia by inhibition ofquorum sensing a randomized controlled trialrdquo Intensive CareMedicine vol 38 no 7 pp 1118ndash1125 2012

[122] A R Smyth P M Cifelli C A Ortori et al ldquoGarlic asan inhibitor of Pseudomonas aeruginosa quorum sensing incystic fibrosisndasha pilot randomized controlled trialrdquo PediatricPulmonology vol 45 no 4 pp 356ndash362 2010

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GenomicsInternational Journal of

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Submit your manuscripts atwwwhindawicom

10 BioMed Research International

al found in their study [100] that the antibody RS2-1G9can bind to 3-oxo-C12-HSL in the extracellular environmentof Pseudomonas aeruginosa thereby attenuating the inflam-matory response of the host XYD-11G2 antibody has beenshown to catalyze the hydrolysis of 3-oxo-C12-HSL signalingthus inhibiting the pyocyanin production by Gram-negativebacteria [101 102] The monoclonal antibody AP4-24H11 wasfound to block the QS signal of Gram-positive Staphylococcusaureus by interfering with AIP IV [103] Another in vivo studyshowed that the antibody AP4-24H11 could significantlyattenuate the tissue necrosis in the infected model [104]Although these monoclonal antibodies have been identifiedto block the QS signaling of pathogenic bacteria (Table 5)their applications for treating bacterial diseases are still in theinitial stage

45 Combinations of Anti-QS Agents and Antibiotics Com-bining use of antibiotic with an anti-QS agent is the mosteffective clinical strategy for the treatment of bacterial dis-eases at present [105 106] Many studies have confirmed thesynergistic effect of antibiotics and anti-QS agents (Table 6)Ajoene furanone c-30 and horseradish extract have beenrevealed to reduce the expression of virulence factors inPseudomonas aeruginosa and make Pseudomonas aeruginosaeasier to be cleared by tobramycin [107ndash111] Another studyhas confirmed the synergistic effects of curcumin gentam-icin and azithromycin on Pseudomonas aeruginosa that isthe expressions of virulence genes were significantly down-regulated by the combining use of curcumin together withgentamicin or azithromycin and the therapeutic doses ofgentamicin and azithromycin were minimized by curcuminsupplementation [112] The anti-QS compounds such asgallocatechin 3-gallate and caffeic acid enhanced therapeuticeffects on Mycoplasma pneumoniae infection by combininguse with tetracycline ciprofloxacin or gentamicin [113 114]N-(2-pyrimidyl) butylamine was confirmed to enhance theantibacterial effect of tobramycin colistin and ciprofloxacinon Pseudomonas aeruginosa [115] Recent studies [116 117]have shown that both farnesol and hamamelitannin canreduce the virulence of Staphylococcus aureus and increasethe sensitivity of Staphylococcus aureus to 120573-lactam antibi-otics Synergistic effects of hamamelitannin baicalin hydratecinnamaldehyde and antibiotics have been demonstrated indifferent infection models [118 119]These findings imply thatcombining use of antibiotics with ant-QS agents has greattherapeutic potential for bacterial diseases

5 Conclusions

Regulating bacterial QS signaling by QS-targeted agents isan effective strategy to control the production of bacte-rial virulence factors and the formation of biofilm Thisnovel nonantibiotic therapy can inhibit the expression ofpathogenic genes prevent infection and reduce the riskof drug resistance of bacterial cells and has been widelyexploited in recent years A large number of studies haveidentified many anti-QS agents to control the pathogenicphenotypes ofmost bacteria and to attenuate the pathological

damage in various animal infection models However mostanti-QS agents are still in the preclinical phase and morehuman clinical trials are warranted to test their practicalfeasibility The results of several existing clinical studies [120ndash122] on anti-QS agents show that compared with antibioticsthe anti-QS compounds may have potential toxicity andtheir therapeutic effect is not as stable as that of antibioticswhich limited their extensive application Combining use ofanti-QS agents with conventional antibiotics can significantlyimprove the efficacy of therapeutic drugs and decrease thecost of human healthcare and is likely to be the mainapplication method of anti-QS agents for bacterial diseasestreatment in the future

Conflicts of Interest

The authors declare that there are no conflicts of interestregarding the publication of this paper

Acknowledgments

The authors are thankful to the China Scholarship Council(CSC) for both financial support and scholarships Theauthors appreciate Dr Ruiqiang Yang at the Nanjing Agri-culture University for his help on this review This workwas supported by the National Natural Science Foundationof China (31472107) the Youth Science Fund Project of theNational Natural Science Foundation of China (31702126)the Chinese Academy of Sciences lsquoHundred Talentrsquo awardthe National Science Foundation for Distinguished YoungScholars of Hunan Province (2016JJ1015) the Postgradu-ate Research and Innovation Project of Hunan Province(CX2017B348) the Hunan Province ldquoHunan Young Scienceand Technology Innovation Talentrdquo Project (2015RS4053)the Hunan Agricultural University Provincial Outstand-ing Doctoral Dissertation Cultivating Fund (YB2017002)and the Open Foundation of Key Laboratory of Agro-ecological Processes in Subtropical Region Institute ofSubtropical Agriculture Chinese Academy of Sciences(ISA2016101)

References

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[2] F E Akram T El-Tayeb K Abou-Aisha and M El-AzizildquoA combination of silver nanoparticles and visible blue lightenhances the antibacterial efficacy of ineffective antibioticsagainst methicillin-resistant Staphylococcus aureus (MRSA)rdquoAnnals of Clinical Microbiology and Antimicrobials vol 15 no1 p 48 2016

[3] L A Barton and M W Simon ldquoProphylactic antibioticsIneffective or inefficaciousrdquo Clinical Pediatrics vol 53 no 8 p813 2014

[4] J Neumaier ldquoAntibiotics are up to 90 ineffective what reallyhelps in common coldsrdquo MMWmdashFortschritte der Medizin vol153 no 3 pp 18-19 2011

BioMed Research International 11

[5] B Schlemmer ldquoBetter prescribing of antibiotics Preventing therisk of ineffective treatment in current infectionrdquo La Revue dupraticien vol 53 no 14 pp 1525-1526 2003

[6] P Stiefelhagen ldquoSuspected severe pneumonia Antibiotics areineffective - what nowrdquo MMWmdashFortschritte der Medizin vol157 no 17 p 28 2015

[7] Z Li and M Knetsch ldquoAntibacterial strategies for wounddressing preventing infection and stimulating healingrdquoCurrentPharmaceutical Design vol 24 no 8 pp 936ndash951 2018

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[9] ldquoMicrobiology by numbersrdquo Nature Reviews Microbiology vol9 no 9 p 628 2011

[10] J P Pearson E C Pesci and B H Iglewski ldquoRoles of Pseu-domonas aeruginosa las and rhl quorum-sensing systems incontrol of elastase and rhamnolipid biosynthesis genesrdquo Journalof Bacteriology vol 179 no 18 pp 5756ndash5767 1997

[11] C Van Delden E C Pesci J P Pearson and B H IglewskildquoStarvation selection restores elastase and rhamnolipid produc-tion in a Pseudomonas aeruginosa quorum-sensing mutantrdquoInfection and Immunity vol 66 no 9 pp 4499ndash4502 1998

[12] L E Dietrich A Price-Whelan A Petersen M Whiteley andD K Newman ldquoThe phenazine pyocyanin is a terminal sig-nalling factor in the quorum sensing network of Pseudomonasaeruginosardquo Molecular Microbiology vol 61 no 5 pp 1308ndash1321 2006

[13] E C Carnes D M Lopez N P Donegan et al ldquoConfinement-induced quorum sensing of individual Staphylococcus aureusbacteriardquoNature Chemical Biology vol 6 no 1 pp 41ndash45 2010

[14] J M Yarwood D J Bartels E M Volper and E P GreenbergldquoQuorum sensing in staphylococcus aureus biofilmsrdquo Journal ofBacteriology vol 186 no 6 pp 1838ndash1850 2004

[15] M J Eickhoff and B L Bassler ldquoSnapShot bacterial quorumsensingrdquo Cell vol 174 no 5 p 1328e1321 2018

[16] M Schuster D Joseph Sexton S P Diggle and E PeterGreenberg ldquoAcyl-homoserine lactone quorum sensing fromevolution to applicationrdquo Annual Review of Microbiology vol67 pp 43ndash63 2013

[17] MH SturmeMKleerebezem J NakayamaA D AkkermansE E Vaugha andWM DeVos ldquoCell to cell communication byautoinducing peptides in gram-positive bacteriardquo Antonie VanLeeuwenhoek vol 81 no 1ndash4 pp 233ndash243 2002

[18] C S Pereira J A Thompson and K B Xavier ldquoAI-2-mediatedsignalling in bacteriardquo FEMS Microbiology Reviews vol 37 no2 pp 156ndash181 2013

[19] M Yang K Sun L Zhou R Yang Z Zhong and J Zhu ldquoFunctional analysis of three AHL autoinducer synthase genes inMesorhizobium loti reveals the important role of quorum sens-ing in symbiotic nodulation rdquoCanadian Journal ofMicrobiologyvol 55 no 2 pp 210ndash214 2009

[20] A Ivanova K Ivanova and T Tzanov ldquoInhibition of Quorum-Sensing A New Paradigm in Controlling Bacterial Virulenceand Biofilm Formationrdquo in Biotechnological Applications ofQuorum Sensing Inhibitors V C Kalia Ed pp 5ndash10 2018

[21] Y Zeng Y Wang Z Yu and Y Huang ldquoHypersensitiveresponse of plasmid-encoded AHL synthase gene to lifestyleand nutrient by Ensifer adhaerens X097rdquo Frontiers in Microbiol-ogy vol 8 p 1160 2017

[22] A O Shpakov ldquoBacterial autoinducing peptidesrdquo Mikrobi-ologiia vol 78 no 3 pp 291ndash303 2009

[23] G J Lyon J S Wright T W Muir and R P Novick ldquoKeydeterminants of receptor activation in the agr autoinducingpeptides of Staphylococcus aureusrdquoBiochemistry vol 41 no 31pp 10095ndash10104 2002

[24] E J Murray and PWilliams ldquoDetection of agr-type autoinduc-ing peptides produced by staphylococcus aureusrdquo Methods inMolecular Biology vol 1673 pp 89ndash96 2018

[25] M J Martin S Clare D Goulding et al ldquoThe agr locus reg-ulates virulence and colonization genes in clostridium difficile027rdquo Journal of Bacteriology vol 195 no 16 pp 3672ndash3681 2013

[26] S Cheraghi L Pourgholi M Shafaati et al ldquoAnalysis ofvirulence genes and accessory gene regulator ( agr ) typesamong methicillin-resistant Staphylococcus aureus strains inIranrdquo Journal of Global Antimicrobial Resistance vol 10 pp 315ndash320 2017

[27] P Gilot G Lina T Cochard and B Poutrel ldquoAnalysis of thegenetic variability of genes encoding the RNA III-activatingcomponents Agr and TRAP in a population of Staphylococcusaureus strains isolated from cows with mastitisrdquo Journal ofClinical Microbiology vol 40 no 11 pp 4060ndash4067 2002

[28] G Lina S Jarraud G Ji et al ldquoTransmembrane topology andhistidine protein kinase activity of AgrC the agr signal receptorin Staphylococcus aureusrdquoMolecular Microbiology vol 28 no3 pp 655ndash662 1998

[29] M Guo S Gamby Y Zheng and H Sintim ldquoSmall moleculeinhibitors of AI-2 signaling in bacteria state-of-the-art andfuture perspectives for anti-quorum sensing agentsrdquo Interna-tional Journal of Molecular Sciences vol 14 no 9 pp 17694ndash17728 2013

[30] JThompson R Oliveira A Djukovic C Ubeda and K XavierldquoManipulation of the quorum sensing signal AI-2 affects theantibiotic-treated gut microbiotardquo Cell Reports vol 10 no 11pp 1861ndash1871 2015

[31] K R Hardie ldquoAutoinducer 2 activity in Escherichia coli culturesupernatants can be actively reduced despite maintenance of anactive synthase LuxSrdquoMicrobiology vol 149 no 3 pp 715ndash7282003

[32] J Wang F Li and Z Tian ldquoRole of microbiota on lunghomeostasis and diseasesrdquo Science China Life Sciences vol 60no 12 pp 1407ndash1415 2017

[33] K Riedel A Gotschlich M Givskov et al ldquoThe cep quorum-sensing system of Burkholderia cepacia H111 controls biofilmformation and swarming motilityrdquoMicrobiology vol 147 no 9pp 2517ndash2528 2001

[34] J C Linnes H Ma and J D Bryers ldquoGiant extracellular matrixbinding protein expression in staphylococcus epidermidis isregulated by biofilm formation and osmotic pressurerdquo CurrentMicrobiology vol 66 no 6 pp 627ndash633 2013

[35] AM Romanı K Fund J Artigas T Schwartz S Sabater andUObst ldquoRelevance of polymeric matrix enzymes during biofilmformationrdquoMicrobial Ecology vol 56 no 3 pp 427ndash436 2008

[36] I Kanwar A K Sah and P K Suresh ldquoBiofilm-mediatedantibiotic-resistant oral bacterial infections mechanism andcombat strategiesrdquo Current Pharmaceutical Design vol 23 no14 pp 2084ndash2095 2017

[37] S Keelara S Thakur and J Patel ldquoBiofilm formation byenvironmental isolates of Salmonella and their sensitivity tonatural antimicrobialsrdquo Foodborne Pathogens and Disease vol13 no 9 pp 509ndash516 2016

[38] F Sepandj H Ceri A Gibb R Read andMOlson ldquoMinimuminhibitory concentration versus minimum biofilm eliminating

12 BioMed Research International

concentration in evaluation of antibiotic sensitivity of entero-cocci causing peritonitisrdquo Peritoneal Dialysis International vol27 no 4 pp 464-465 2007

[39] B A Niemira and E B Solomon ldquoSensitivity of planktonicand biofilm-associated salmonella spp to ionizing radiationrdquoApplied andEnvironmentalMicrobiology vol 71 no 5 pp 2732ndash2736 2005

[40] A M Gamage G Shui M R Wenk and K L Chua ldquoN-Octanoylhomoserine lactone signalling mediated by the BpsI-BpsR quorum sensing system plays a major role in biofilmformationofBurkholderia pseudomalleirdquoMicrobiology vol 157no 4 pp 1176ndash1186 2011

[41] S H Hong M Hegde J Kim X Wang A Jayaraman andT K Wood ldquoSynthetic quorum-sensing circuit to controlconsortial biofilm formation and dispersal in a microfluidicdevicerdquo Nature Communications vol 3 p 613 2012

[42] P Sankar Ganesh and V Ravishankar Rai ldquoAttenuation ofquorum-sensing-dependent virulence factors and biofilm for-mation by medicinal plants against antibiotic resistant Pseu-domonas aeruginosardquo Journal of Traditional and Complemen-tary Medicine vol 8 no 1 pp 170ndash177 2018

[43] P Shih ldquoEffects of quorum-sensing deficiency on Pseudomonasaeruginosa biofilm formation and antibiotic resistancerdquo Journalof Antimicrobial Chemotherapy vol 49 no 2 pp 309ndash314

[44] M I Chernukha I A Shaginian IM Romanova G VMaleevand A L Gintsburg ldquoThe role of ldquoquorum sensingrdquo regula-tion system in symbiotic interaction of bacteria Burkholderiacepacia and Pseudomonas aeruginosa during mixed infectionrdquoZhurnalMikrobiologii Epidemiologii Immunobiologii no 4 pp32ndash37 2006

[45] F M Husain I Ahmad A S Al-Thubiani H H AbulreeshI M AlHazza and F Aqil ldquoLeaf extracts of Mangifera indicaL inhibit quorum sensing - Regulated production of virulencefactors and biofilm in test bacteriardquo Frontiers in Microbiologyvol 8 p 727 2017

[46] D G Renter J G Morris J M Sargeant et al ldquoPreva-lence risk factors O serogroups and virulence profiles ofshiga toxinndashproducing bacteria from cattle production environ-mentsrdquo Journal of Food Protection vol 68 no 8 pp 1556ndash15652005

[47] A R Hauser ldquoPseudomonas aeruginosa So many virulencefactors so little timerdquo Critical Care Medicine vol 39 no 9 pp2193-2194 2011

[48] R Le Berre S Nguyen E Nowak et al ldquoRelative contributionof three main virulence factors in Pseudomonas aeruginosapneumoniardquo Critical Care Medicine vol 39 no 9 pp 2113ndash2120 2011

[49] M M Gallardo-Garcia G Sanchez-Espin R Ivanova-Georgieva et al ldquoRelationship between pathogenic clinicaland virulence factors of Staphylococcus aureus in infectiveendocarditis versus uncomplicated bacteremia a case-controlstudyrdquo European Journal of Clinical Microbiology amp InfectiousDiseases vol 35 no 5 pp 821ndash828 2016

[50] F Sabouni S Mahmoudi A Bahador et al ldquoVirulence factorsof staphylococcus aureus isolates in an iranian referral childrenrsquoshospitalrdquo Osong Public Health and Research Perspectives vol 5no 2 pp 96ndash100 2014

[51] H M Aboushleib H M Omar R Abozahra A Elsheredyand K Baraka ldquoCorrelation of quorum sensing and virulencefactors in Pseudomonas aeruginosa isolates in Egyptrdquo TheJournal of Infection in Developing Countries vol 9 no 10 pp1091ndash1099 2015

[52] R T Sturbelle L F Avila T B Roos et al ldquoThe role ofquorum sensing in Escherichia coli (ETEC) virulence factorsrdquoVeterinary Microbiology vol 180 no 3-4 pp 245ndash252 2015

[53] J E Paczkowski S Mukherjee A R McCready et alldquoFlavonoids suppress Pseudomonas aeruginosa Virulencethrough allosteric inhibition of quorum-sensing receptorsrdquoTheJournal of Biological Chemistry vol 292 no 10 pp 4064ndash40762017

[54] L Weng Y Yang Y Zhang and L Wang ldquoA new syntheticligand that activatesQscRand blocks antibiotic-tolerant biofilmformation in Pseudomonas aeruginosardquo Applied Microbiologyand Biotechnology vol 98 no 6 pp 2565ndash2572 2014

[55] Y-X Yang Z-H Xu Y-Q Zhang J Tian L-X Wengand L-H Wang ldquoA new quorum-sensing inhibitor attenuatesvirulence and decreases antibiotic resistance in Pseudomonasaeruginosardquo Journal of Microbiology vol 50 no 6 pp 987ndash9932012

[56] J N Capilato S V Philippi T Reardon et al ldquoDevelopment ofa novel series of non-natural triaryl agonists and antagonists ofthe Pseudomonas aeruginosa LasR quorum sensing receptorrdquoBioorganic amp Medicinal Chemistry vol 25 no 1 pp 153ndash1652017

[57] C T OrsquoLoughlin L C Miller A Siryaporn K Drescher MF Semmelhack and B L Bassler ldquoA quorum-sensing inhibitorblocks Pseudomonas aeruginosa virulence and biofilm forma-tionrdquo Proceedings of the National Acadamy of Sciences of theUnited States of America vol 110 no 44 pp 17981ndash17986 2013

[58] G D Geske J C OrsquoNeill D M Miller M E Mattmannand H E Blackwell ldquoModulation of bacterial quorum sensingwith synthetic ligands systematic evaluation of N-acylatedhomoserine lactones in multiple species and new insights intotheir mechanisms of actionrdquo Journal of the American ChemicalSociety vol 129 no 44 pp 13613ndash13625 2007

[59] B K Khajanchi M L Kirtley S M Brackman A KChopra and B A McCormick ldquoImmunomodulatory and pro-tective roles of quorum-sensing signaling molecules N-acylhomoserine lactones during infection of mice with aeromonashydrophilardquo Infection and Immunity vol 79 no 7 pp 2646ndash2657 2011

[60] H Tomioka C Sano and Y Tatano ldquoHost-directed therapeu-tics against mycobacterial infectionsrdquo Current PharmaceuticalDesign vol 23 no 18 pp 2644ndash2656 2017

[61] M R Parsek D L Val B L Hanzelka J E Cronan Jr and EP Greenberg ldquoAcyl homoserine-lactone quorum-sensing signalgenerationrdquo Proceedings of the National Acadamy of Sciences ofthe United States of America vol 96 no 8 pp 4360ndash4365 1999

[62] MK Yadav SW Park SW Chae and J J Song ldquoSinefungin anatural nucleoside analogue of S-adenosylmethionine inhibitsStreptococcus pneumoniae biofilm growthrdquo BioMed ResearchInternational vol 2014 Article ID 156987 10 pages 2014

[63] M Hentzer and M Givskov ldquoPharmacological inhibition ofquorum sensing for the treatment of chronic bacterial infec-tionsrdquo The Journal of Clinical Investigation vol 112 no 9 pp1300ndash1307 2003

[64] V Singh G B Evans D H Lenz et al ldquoFemtomolar tran-sition state analogue inhibitors of 5rsquo-methylthioadenosineS-adenosylhomocysteine nucleosidase fromEscherichia colirdquoTheJournal of Biological Chemistry vol 280 no 18 pp 18265ndash182732005

[65] A Priyadarshi E E Kim and K Y Hwang ldquo Structuralinsights into Staphylococcus aureus enoyl-ACP reductase (FabI)

BioMed Research International 13

in complex with NADP and triclosan rdquo Proteins StructureFunction and Bioinformatics vol 78 no 2 pp 480ndash486 2010

[66] N Surolia and A Surolia ldquoTriclosan offers protection againstblood stages of malaria by inhibiting enoyl-ACP reductase ofPlasmodium falciparumrdquoNatureMedicine vol 7 no 2 pp 167ndash173 2001

[67] E Krol and A Becker ldquoRhizobial homologs of the fattyacid transporter FadL facilitate perception of long-chainacyl-homoserine lactone signalsrdquo Proceedings of the NationalAcadamy of Sciences of the United States of America vol 111 no29 pp 10702ndash10707 2014

[68] J L Copitch R N Whitehead and M A Webber ldquoPrevalenceof decreased susceptibility to triclosan in Salmonella entericaisolates fromanimals andhumans andassociationwithmultipledrug resistancerdquo International Journal of Antimicrobial Agentsvol 36 no 3 pp 247ndash251 2010

[69] S Lu N Wang S Ma X Hu L Kang and Y Yu ldquoParabensand triclosan in shellfish fromShenzhen coastal waters bioindi-cation of pollution and human health risksrdquo EnvironmentalPollution vol 246 pp 257ndash263 2018

[70] N Huma P Shankar J Kushwah et al ldquoDiversity and poly-morphism in AHL-Lactonase gene (aiiA) of Bacillusrdquo Journalof Microbiology and Biotechnology vol 21 no 10 pp 1001ndash10112011

[71] S Y Park B J Hwang M Shin J Kim H Kim and J LeeldquoN-acylhomoserine lactonase-producingRhodococcussppwithdifferent AHL-degrading activitiesrdquo FEMSMicrobiology Lettersvol 261 no 1 pp 102ndash108 2006

[72] A Guendouze L Plener J Bzdrenga et al ldquoEffect of quo-rum quenching lactonase in clinical isolates of pseudomonasaeruginosa and comparison with quorum sensing inhibitorsrdquoFrontiers in Microbiology vol 8 p 227 2017

[73] S Hraiech J Hiblot J Lafleur et al ldquoInhaled lactonase reducespseudomonas aeruginosa quorum sensing and mortality in ratpneumoniardquo PLoS ONE vol 9 no 10 Article ID e107125 2014

[74] J Y Chow Y Yang S B Tay K L Chua and W S YewldquoDisruption of biofilm formation by the human pathogenacinetobacter baumannii using engineered quorum-quenchinglactonasesrdquoAntimicrobial Agents andChemotherapy vol 58 no3 pp 1802ndash1805 2014

[75] X FanM Liang L Wang R Chen H Li and X Liu ldquoAii810 anovel cold-adapted N-acylhomoserine lactonase discovered inametagenome can strongly attenuate Pseudomonas aeruginosavirulence factors and biofilm formationrdquo Frontiers in Microbiol-ogy vol 8 p 1950 2017

[76] MM Sakr KM AboshanabW F ElkhatibMA Yassien andN AHassouna ldquoOverexpressed recombinant quorumquench-ing lactonase reduces the virulence motility and biofilm for-mationofmultidrug-resistant Pseudomonas aeruginosa clinicalisolatesrdquo Appl Microbiol Biotechnol vol 102 no 24 pp 10613ndash10622 2018

[77] C Schipper C Hornung P Bijtenhoorn M Quitschau SGrond andW R Streit ldquoMetagenome-derived clones encodingtwo novel lactonase family proteins involved in biofilm inhibi-tion in pseudomonas aeruginosardquo Applied and EnvironmentalMicrobiology vol 75 no 1 pp 224ndash233 2008

[78] W Dong J Zhu X Guo et al ldquoCharacterization of AiiKan AHL lactonase from Kurthia huakui LAM0618T and itsapplication in quorum quenching on Pseudomonas aeruginosaPAO1rdquo Scientific Reports vol 8 no 1 p 6013 2018

[79] W Liu C Ran Z Liu et al ldquoEffects of dietary Lactobacillusplantarum and AHL lactonase on the control of Aeromonas

hydrophila infection in tilapiardquoMicrobiologyopen vol 5 no 4pp 687ndash699 2016

[80] M Torres J C Reina J C Fuentes-Monteverde et al ldquoAHL-lactonase expression in three marine emerging pathogenicVibrio spp reduces virulence and mortality in brine shrimp(Artemia salina) and Manila clam (Venerupis philippinarum)rdquoPLoS ONE vol 13 no 4 Article ID e0195176 2018

[81] G Vinoj B Vaseeharan S Thomas A J Spiers and S ShanthildquoQuorum-quenching activity of the AHL-lactonase from bacil-lus licheniformis DAHB1 inhibits vibrio biofilm formation invitro and reduces shrimp intestinal colonisation andmortalityrdquoMarine Biotechnology vol 16 no 6 pp 707ndash715 2014

[82] V C Kalia ldquoIn search of versatile organisms for quorum-sensing inhibitors acyl homoserine lactones (AHL)-acylaseand AHL-lactonaserdquo FEMS Microbiology Letters vol 359 no2 p 143 2014

[83] V B Maisuria and A S Nerurkar ldquoInterference of quorumsensing by Delftia sp VM4 depends on the activity of a noveln-acylhomoserine lactone-acylaserdquo PLoS ONE vol 10 no 9Article ID e0138034 2015

[84] R Mukherji N K Varshney P Panigrahi C Suresh and APrabhune ldquoA new role for penicillin acylases degradation ofacyl homoserine lactone quorum sensing signals by Kluyveracitrophila penicillin G acylaserdquo Enzyme and Microbial Technol-ogy vol 56 pp 1ndash7 2014

[85] C F Sio L G Otten R H Cool et al ldquoQuorum quenchingby an N-acyl-homoserine lactone acylase from Pseudomonasaeruginosa PAO1rdquo Infection and Immunity vol 74 no 3 pp1673ndash1682 2006

[86] K Ivanova M M Fernandes E Mendoza and T TzanovldquoEnzyme multilayer coatings inhibit Pseudomonas aeruginosabiofilm formation on urinary cathetersrdquo Applied Microbiologyand Biotechnology vol 99 no 10 pp 4373ndash4385 2015

[87] N Grover J G Plaks S R Summers G R Chado M J Schurrand J L Kaar ldquoAcylase-containing polyurethane coatings withanti-biofilm activityrdquo Biotechnology and Bioengineering vol 113no 12 pp 2535ndash2543 2016

[88] J Lee I Lee J Nam D S Hwang K-M Yeon and JKim ldquoImmobilization and stabilization of acylase on carboxy-lated polyaniline nanofibers for highly effective antifoulingapplication via quorum quenchingrdquo ACS Applied Materials ampInterfaces vol 9 no 18 pp 15424ndash15432 2017

[89] S Uroz S R Chhabra M Camara P Williams P Ogerand Y Dessaux ldquoN-acylhomoserine lactone quorum-sensingmolecules are modified and degraded by Rhodococcus ery-thropolis W2 by both amidolytic and novel oxidoreductaseactivitiesrdquoMicrobiology vol 151 no 10 pp 3313ndash3322 2005

[90] B Eva and S Maria ldquoMicrobial secondary metabolites asinhibitors of pharmaceutically important transferases and oxi-doreductasesrdquo Ceska Slov Farm vol 61 no 3 pp 107ndash114 2012

[91] P Bijtenhoorn H Mayerhofer J Muller-Dieckmann et alldquoA novel metagenomic Short-Chain dehydrogenasereductaseattenuates pseudomonas Aeruginosa biofilm formation andvirulence on Caenorhabditis elegansrdquo PLoS ONE vol 6 no 10Article ID e26278 2011

[92] J D Wildschut R M Lang J K Voordouw and G Voor-douw ldquoRubredoxin oxygen oxidoreductase enhances survivalof desulfovibrio vulgaris hildenborough under microaerophilicconditionsrdquo Journal of Bacteriology vol 188 no 17 pp 6253ndash6260 2006

14 BioMed Research International

[93] X Zhang S Ou-yang JWang L Liao RWu and JWei ldquoCon-struction of antibacterial surface via layer-by-layer methodrdquoCurrent Pharmaceutical Design vol 24 no 8 pp 926ndash935 2018

[94] C Pustelny A Albers K Buldt-Karentzopoulos et al ldquoDiox-ygenase-mediated quenching of quinolone-dependent quorumsensing in pseudomonas aeruginosardquoChemistry amp Biology vol16 no 12 pp 1259ndash1267 2009

[95] J T Hodgkinson W R Galloway M Welch and DR Spring ldquoMicrowave-assisted preparation of the quorum-sensing molecule 2-heptyl-3-hydroxy-4(1H)-quinolone andstructurally related analogsrdquo Nature Protocols vol 7 no 6 pp1184ndash1192 2012

[96] F Witzgall T Depke M Hoffmann et al ldquoThe alkylquinolonerepertoire of Pseudomonas aeruginosa is linked to structuralflexibility of the fabh-like 2-heptyl-3-hydroxy-4(1H)-quinolone(PQS) biosynthesis enzyme PqsBCrdquo ChemBioChem vol 19 no14 pp 1531ndash1544 2018

[97] L Andresen E Sala V Koiv and A Mae ldquoA role for theRcs phosphorelay in regulating expression of plant cell walldegrading enzymes in Pectobacterium carotovorum subspcarotovorumrdquoMicrobiology vol 156 no 5 pp 1323ndash1334 2010

[98] L Andresen V Koiv T Alamae and A Mae ldquoThe Rcs phos-phorelay modulates the expression of plant cell wall degradingenzymes and virulence in Pectobacterium carotovorum sspcarotovorumrdquo FEMS Microbiology Letters vol 273 no 2 pp229ndash238 2007

[99] R K Gupta S Chhibber and K Harjai ldquoAcyl homoserinelactones from culture supernatants of pseudomonas aeruginosaaccelerate host immunomodulationrdquo PLoS ONE vol 6 no 6Article ID e20860 2011

[100] G F Kaufmann J Park J M Mee R J Ulevitch and KD Janda ldquoThe quorum quenching antibody RS2-1G9 protectsmacrophages from the cytotoxic effects of the Pseudomonasaeruginosa quorum sensing signalling molecule N-3-oxo-dodecanoyl-homoserine lactonerdquo Molecular Immunology vol45 no 9 pp 2710ndash2714 2008

[101] S Koul J Prakash A Mishra and V C Kalia ldquoPotential emer-gence of multi-quorum sensing inhibitor resistant (MQSIR)bacteriardquo Indian Journal of Microbiology vol 56 no 1 pp 1ndash182016

[102] T Praneenararat A G Palmer and H E Blackwell ldquoChemicalmethods to interrogate bacterial quorum sensing pathwaysrdquoOrganicampBiomolecular Chemistry vol 10 no 41 pp 8189ndash81992012

[103] J Park R Jagasia G F Kaufmann et al ldquoInfection controlby antibody disruption of bacterial quorum sensing signalingrdquoChemistry amp Biology vol 14 no 10 pp 1119ndash1127 2007

[104] C Grandclement M Tannieres S Morera Y Dessaux DFaure andM Camara ldquoQuorum quenching role in nature andapplied developmentsrdquo FEMSMicrobiology Reviews vol 40 no1 pp 86ndash116 2016

[105] MHan J GuG F Gao andW J Liu ldquoChina in action nationalstrategies to combat against emerging infectious diseasesrdquoScience China Life Sciences vol 60 no 12 pp 1383ndash1385 2017

[106] J Liu H Yu Y Huang et al ldquoComplete genome sequence ofa novel bacteriophage infecting Bradyrhizobium diazoefficiensUSDA110rdquo Science China Life Sciences vol 61 no 1 pp 118ndash1212018

[107] L D Christensen M van Gennip T H Jakobsen et alldquoSynergistic antibacterial efficacy of early combination treat-ment with tobramycin and quorum-sensing inhibitors against

Pseudomonas aeruginosa in an intraperitoneal foreign-bodyinfection mouse modelrdquo Journal of Antimicrobial Chemother-apy vol 67 no 5 pp 1198ndash1206 2012

[108] J Fong M Yuan T H Jakobsen et al ldquoDisulfide bond-containing ajoene analogues as novel quorum sensinginhibitors of Pseudomonas aeruginosardquo Journal of MedicinalChemistry vol 60 no 1 pp 215ndash227 2017

[109] R Garcıa-Contreras M Martınez-Vazquez N VelazquezGuadarrama et al ldquo Resistance to the quorum-quenchingcompounds brominated furanone C-30 and 5-fluorouracil inPseudomonas aeruginosa clinical isolates rdquo Pathogens and Dis-ease vol 68 no 1 pp 8ndash11 2013

[110] T H Jakobsen S K Bragason R K Phipps et al ldquoFood as asource for quorum sensing inhibitors iberin from horseradishrevealed as a quorum sensing inhibitor of pseudomonas aerug-inosardquo Applied and Environmental Microbiology vol 78 no 7pp 2410ndash2421 2012

[111] A Vadekeetil H Saini S Chhibber and K Harjai ldquo Exploitingthe antivirulence efficacy of an ajoene-ciprofloxacin combina-tion against Pseudomonas aeruginosa biofilm associatedmurineacute pyelonephritis rdquo Biofouling vol 32 no 4 pp 371ndash3822016

[112] S Bahari H Zeighami H Mirshahabi S Roudashti and FHaghi ldquoInhibition of pseudomonas aeruginosa quorum sensingby subinhibitory concentrations of curcumin with gentamicinand azithromycinrdquo Journal of Global Antimicrobial Resistancevol 10 pp 21ndash28 2017

[113] A S Roccaro A R Blanco F Giuliano D Rusciano and VEnea ldquoEpigallocatechin-gallate enhances the activity of tetra-cycline in staphylococci by inhibiting its efflux from bacterialcellsrdquo Antimicrobial Agents and Chemotherapy vol 48 no 6pp 1968ndash1973 2004

[114] C Chu J Deng Y Man and Y Qu ldquoGreen tea extractsepigallocatechin-3-gallate for different treatmentsrdquo BioMedResearch International vol 2017 Article ID 5615647 9 pages2017

[115] A Furiga B Lajoie S El Hage G Baziard and C RoquesldquoImpairment of pseudomonas aeruginosa biofilm resistance toantibiotics by combining the drugs with a new quorum-sensinginhibitorrdquo Antimicrobial Agents and Chemotherapy vol 60 no3 pp 1676ndash1686 2016

[116] Y Inoue N Togashi and H Hamashima ldquoFarnesol-induceddisruption of the staphylococcus aureus cytoplasmic mem-branerdquo Biological and Pharmaceutical Bulletin vol 39 no 5 pp653ndash656 2016

[117] C Kim D Hesek M Lee and S Mobashery ldquoPotentiationof the activity of beta-lactam antibiotics by farnesol and itsderivativesrdquo Bioorganic amp Medicinal Chemistry Letters vol 28no 4 pp 642ndash645 2018

[118] G Brackman P Cos L Maes H J Nelis and T Coenye ldquoQuo-rum sensing inhibitors increase the susceptibility of bacterialbiofilms to antibiotics in vitro and in vivordquoAntimicrobial Agentsand Chemotherapy vol 55 no 6 pp 2655ndash2661 2011

[119] G Brackman K Breyne R De Rycke et al ldquoThe quorum sens-ing inhibitor hamamelitannin increases antibiotic susceptibilityof staphylococcus aureus biofilms by affecting peptidoglycanbiosynthesis and eDNA releaserdquo Scientific Reports vol 6 ArticleID 20321 2016

[120] J M Walz R L Avelar K J Longtine K L Carter L A Mer-mel and S O Heard ldquoAnti-infective external coating of centralvenous catheters A randomized noninferiority trial comparing

BioMed Research International 15

5-fluorouracil with chlorhexidinesilver sulfadiazine in pre-venting catheter colonizationrdquo Critical Care Medicine vol 38no 11 pp 2095ndash2102 2010

[121] C van Delden T Kohler F Brunner-Ferber B Francois JCarlet and J Pechere ldquoAzithromycin to prevent Pseudomonasaeruginosa ventilator-associated pneumonia by inhibition ofquorum sensing a randomized controlled trialrdquo Intensive CareMedicine vol 38 no 7 pp 1118ndash1125 2012

[122] A R Smyth P M Cifelli C A Ortori et al ldquoGarlic asan inhibitor of Pseudomonas aeruginosa quorum sensing incystic fibrosisndasha pilot randomized controlled trialrdquo PediatricPulmonology vol 45 no 4 pp 356ndash362 2010

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Submit your manuscripts atwwwhindawicom

BioMed Research International 11

[5] B Schlemmer ldquoBetter prescribing of antibiotics Preventing therisk of ineffective treatment in current infectionrdquo La Revue dupraticien vol 53 no 14 pp 1525-1526 2003

[6] P Stiefelhagen ldquoSuspected severe pneumonia Antibiotics areineffective - what nowrdquo MMWmdashFortschritte der Medizin vol157 no 17 p 28 2015

[7] Z Li and M Knetsch ldquoAntibacterial strategies for wounddressing preventing infection and stimulating healingrdquoCurrentPharmaceutical Design vol 24 no 8 pp 936ndash951 2018

[8] W Xu S Dong Y Han S Li and Y Liu ldquoHydrogels asantibacterial biomaterialsrdquo Current Pharmaceutical Design vol24 no 8 pp 843ndash854 2018

[9] ldquoMicrobiology by numbersrdquo Nature Reviews Microbiology vol9 no 9 p 628 2011

[10] J P Pearson E C Pesci and B H Iglewski ldquoRoles of Pseu-domonas aeruginosa las and rhl quorum-sensing systems incontrol of elastase and rhamnolipid biosynthesis genesrdquo Journalof Bacteriology vol 179 no 18 pp 5756ndash5767 1997

[11] C Van Delden E C Pesci J P Pearson and B H IglewskildquoStarvation selection restores elastase and rhamnolipid produc-tion in a Pseudomonas aeruginosa quorum-sensing mutantrdquoInfection and Immunity vol 66 no 9 pp 4499ndash4502 1998

[12] L E Dietrich A Price-Whelan A Petersen M Whiteley andD K Newman ldquoThe phenazine pyocyanin is a terminal sig-nalling factor in the quorum sensing network of Pseudomonasaeruginosardquo Molecular Microbiology vol 61 no 5 pp 1308ndash1321 2006

[13] E C Carnes D M Lopez N P Donegan et al ldquoConfinement-induced quorum sensing of individual Staphylococcus aureusbacteriardquoNature Chemical Biology vol 6 no 1 pp 41ndash45 2010

[14] J M Yarwood D J Bartels E M Volper and E P GreenbergldquoQuorum sensing in staphylococcus aureus biofilmsrdquo Journal ofBacteriology vol 186 no 6 pp 1838ndash1850 2004

[15] M J Eickhoff and B L Bassler ldquoSnapShot bacterial quorumsensingrdquo Cell vol 174 no 5 p 1328e1321 2018

[16] M Schuster D Joseph Sexton S P Diggle and E PeterGreenberg ldquoAcyl-homoserine lactone quorum sensing fromevolution to applicationrdquo Annual Review of Microbiology vol67 pp 43ndash63 2013

[17] MH SturmeMKleerebezem J NakayamaA D AkkermansE E Vaugha andWM DeVos ldquoCell to cell communication byautoinducing peptides in gram-positive bacteriardquo Antonie VanLeeuwenhoek vol 81 no 1ndash4 pp 233ndash243 2002

[18] C S Pereira J A Thompson and K B Xavier ldquoAI-2-mediatedsignalling in bacteriardquo FEMS Microbiology Reviews vol 37 no2 pp 156ndash181 2013

[19] M Yang K Sun L Zhou R Yang Z Zhong and J Zhu ldquoFunctional analysis of three AHL autoinducer synthase genes inMesorhizobium loti reveals the important role of quorum sens-ing in symbiotic nodulation rdquoCanadian Journal ofMicrobiologyvol 55 no 2 pp 210ndash214 2009

[20] A Ivanova K Ivanova and T Tzanov ldquoInhibition of Quorum-Sensing A New Paradigm in Controlling Bacterial Virulenceand Biofilm Formationrdquo in Biotechnological Applications ofQuorum Sensing Inhibitors V C Kalia Ed pp 5ndash10 2018

[21] Y Zeng Y Wang Z Yu and Y Huang ldquoHypersensitiveresponse of plasmid-encoded AHL synthase gene to lifestyleand nutrient by Ensifer adhaerens X097rdquo Frontiers in Microbiol-ogy vol 8 p 1160 2017

[22] A O Shpakov ldquoBacterial autoinducing peptidesrdquo Mikrobi-ologiia vol 78 no 3 pp 291ndash303 2009

[23] G J Lyon J S Wright T W Muir and R P Novick ldquoKeydeterminants of receptor activation in the agr autoinducingpeptides of Staphylococcus aureusrdquoBiochemistry vol 41 no 31pp 10095ndash10104 2002

[24] E J Murray and PWilliams ldquoDetection of agr-type autoinduc-ing peptides produced by staphylococcus aureusrdquo Methods inMolecular Biology vol 1673 pp 89ndash96 2018

[25] M J Martin S Clare D Goulding et al ldquoThe agr locus reg-ulates virulence and colonization genes in clostridium difficile027rdquo Journal of Bacteriology vol 195 no 16 pp 3672ndash3681 2013

[26] S Cheraghi L Pourgholi M Shafaati et al ldquoAnalysis ofvirulence genes and accessory gene regulator ( agr ) typesamong methicillin-resistant Staphylococcus aureus strains inIranrdquo Journal of Global Antimicrobial Resistance vol 10 pp 315ndash320 2017

[27] P Gilot G Lina T Cochard and B Poutrel ldquoAnalysis of thegenetic variability of genes encoding the RNA III-activatingcomponents Agr and TRAP in a population of Staphylococcusaureus strains isolated from cows with mastitisrdquo Journal ofClinical Microbiology vol 40 no 11 pp 4060ndash4067 2002

[28] G Lina S Jarraud G Ji et al ldquoTransmembrane topology andhistidine protein kinase activity of AgrC the agr signal receptorin Staphylococcus aureusrdquoMolecular Microbiology vol 28 no3 pp 655ndash662 1998

[29] M Guo S Gamby Y Zheng and H Sintim ldquoSmall moleculeinhibitors of AI-2 signaling in bacteria state-of-the-art andfuture perspectives for anti-quorum sensing agentsrdquo Interna-tional Journal of Molecular Sciences vol 14 no 9 pp 17694ndash17728 2013

[30] JThompson R Oliveira A Djukovic C Ubeda and K XavierldquoManipulation of the quorum sensing signal AI-2 affects theantibiotic-treated gut microbiotardquo Cell Reports vol 10 no 11pp 1861ndash1871 2015

[31] K R Hardie ldquoAutoinducer 2 activity in Escherichia coli culturesupernatants can be actively reduced despite maintenance of anactive synthase LuxSrdquoMicrobiology vol 149 no 3 pp 715ndash7282003

[32] J Wang F Li and Z Tian ldquoRole of microbiota on lunghomeostasis and diseasesrdquo Science China Life Sciences vol 60no 12 pp 1407ndash1415 2017

[33] K Riedel A Gotschlich M Givskov et al ldquoThe cep quorum-sensing system of Burkholderia cepacia H111 controls biofilmformation and swarming motilityrdquoMicrobiology vol 147 no 9pp 2517ndash2528 2001

[34] J C Linnes H Ma and J D Bryers ldquoGiant extracellular matrixbinding protein expression in staphylococcus epidermidis isregulated by biofilm formation and osmotic pressurerdquo CurrentMicrobiology vol 66 no 6 pp 627ndash633 2013

[35] AM Romanı K Fund J Artigas T Schwartz S Sabater andUObst ldquoRelevance of polymeric matrix enzymes during biofilmformationrdquoMicrobial Ecology vol 56 no 3 pp 427ndash436 2008

[36] I Kanwar A K Sah and P K Suresh ldquoBiofilm-mediatedantibiotic-resistant oral bacterial infections mechanism andcombat strategiesrdquo Current Pharmaceutical Design vol 23 no14 pp 2084ndash2095 2017

[37] S Keelara S Thakur and J Patel ldquoBiofilm formation byenvironmental isolates of Salmonella and their sensitivity tonatural antimicrobialsrdquo Foodborne Pathogens and Disease vol13 no 9 pp 509ndash516 2016

[38] F Sepandj H Ceri A Gibb R Read andMOlson ldquoMinimuminhibitory concentration versus minimum biofilm eliminating

12 BioMed Research International

concentration in evaluation of antibiotic sensitivity of entero-cocci causing peritonitisrdquo Peritoneal Dialysis International vol27 no 4 pp 464-465 2007

[39] B A Niemira and E B Solomon ldquoSensitivity of planktonicand biofilm-associated salmonella spp to ionizing radiationrdquoApplied andEnvironmentalMicrobiology vol 71 no 5 pp 2732ndash2736 2005

[40] A M Gamage G Shui M R Wenk and K L Chua ldquoN-Octanoylhomoserine lactone signalling mediated by the BpsI-BpsR quorum sensing system plays a major role in biofilmformationofBurkholderia pseudomalleirdquoMicrobiology vol 157no 4 pp 1176ndash1186 2011

[41] S H Hong M Hegde J Kim X Wang A Jayaraman andT K Wood ldquoSynthetic quorum-sensing circuit to controlconsortial biofilm formation and dispersal in a microfluidicdevicerdquo Nature Communications vol 3 p 613 2012

[42] P Sankar Ganesh and V Ravishankar Rai ldquoAttenuation ofquorum-sensing-dependent virulence factors and biofilm for-mation by medicinal plants against antibiotic resistant Pseu-domonas aeruginosardquo Journal of Traditional and Complemen-tary Medicine vol 8 no 1 pp 170ndash177 2018

[43] P Shih ldquoEffects of quorum-sensing deficiency on Pseudomonasaeruginosa biofilm formation and antibiotic resistancerdquo Journalof Antimicrobial Chemotherapy vol 49 no 2 pp 309ndash314

[44] M I Chernukha I A Shaginian IM Romanova G VMaleevand A L Gintsburg ldquoThe role of ldquoquorum sensingrdquo regula-tion system in symbiotic interaction of bacteria Burkholderiacepacia and Pseudomonas aeruginosa during mixed infectionrdquoZhurnalMikrobiologii Epidemiologii Immunobiologii no 4 pp32ndash37 2006

[45] F M Husain I Ahmad A S Al-Thubiani H H AbulreeshI M AlHazza and F Aqil ldquoLeaf extracts of Mangifera indicaL inhibit quorum sensing - Regulated production of virulencefactors and biofilm in test bacteriardquo Frontiers in Microbiologyvol 8 p 727 2017

[46] D G Renter J G Morris J M Sargeant et al ldquoPreva-lence risk factors O serogroups and virulence profiles ofshiga toxinndashproducing bacteria from cattle production environ-mentsrdquo Journal of Food Protection vol 68 no 8 pp 1556ndash15652005

[47] A R Hauser ldquoPseudomonas aeruginosa So many virulencefactors so little timerdquo Critical Care Medicine vol 39 no 9 pp2193-2194 2011

[48] R Le Berre S Nguyen E Nowak et al ldquoRelative contributionof three main virulence factors in Pseudomonas aeruginosapneumoniardquo Critical Care Medicine vol 39 no 9 pp 2113ndash2120 2011

[49] M M Gallardo-Garcia G Sanchez-Espin R Ivanova-Georgieva et al ldquoRelationship between pathogenic clinicaland virulence factors of Staphylococcus aureus in infectiveendocarditis versus uncomplicated bacteremia a case-controlstudyrdquo European Journal of Clinical Microbiology amp InfectiousDiseases vol 35 no 5 pp 821ndash828 2016

[50] F Sabouni S Mahmoudi A Bahador et al ldquoVirulence factorsof staphylococcus aureus isolates in an iranian referral childrenrsquoshospitalrdquo Osong Public Health and Research Perspectives vol 5no 2 pp 96ndash100 2014

[51] H M Aboushleib H M Omar R Abozahra A Elsheredyand K Baraka ldquoCorrelation of quorum sensing and virulencefactors in Pseudomonas aeruginosa isolates in Egyptrdquo TheJournal of Infection in Developing Countries vol 9 no 10 pp1091ndash1099 2015

[52] R T Sturbelle L F Avila T B Roos et al ldquoThe role ofquorum sensing in Escherichia coli (ETEC) virulence factorsrdquoVeterinary Microbiology vol 180 no 3-4 pp 245ndash252 2015

[53] J E Paczkowski S Mukherjee A R McCready et alldquoFlavonoids suppress Pseudomonas aeruginosa Virulencethrough allosteric inhibition of quorum-sensing receptorsrdquoTheJournal of Biological Chemistry vol 292 no 10 pp 4064ndash40762017

[54] L Weng Y Yang Y Zhang and L Wang ldquoA new syntheticligand that activatesQscRand blocks antibiotic-tolerant biofilmformation in Pseudomonas aeruginosardquo Applied Microbiologyand Biotechnology vol 98 no 6 pp 2565ndash2572 2014

[55] Y-X Yang Z-H Xu Y-Q Zhang J Tian L-X Wengand L-H Wang ldquoA new quorum-sensing inhibitor attenuatesvirulence and decreases antibiotic resistance in Pseudomonasaeruginosardquo Journal of Microbiology vol 50 no 6 pp 987ndash9932012

[56] J N Capilato S V Philippi T Reardon et al ldquoDevelopment ofa novel series of non-natural triaryl agonists and antagonists ofthe Pseudomonas aeruginosa LasR quorum sensing receptorrdquoBioorganic amp Medicinal Chemistry vol 25 no 1 pp 153ndash1652017

[57] C T OrsquoLoughlin L C Miller A Siryaporn K Drescher MF Semmelhack and B L Bassler ldquoA quorum-sensing inhibitorblocks Pseudomonas aeruginosa virulence and biofilm forma-tionrdquo Proceedings of the National Acadamy of Sciences of theUnited States of America vol 110 no 44 pp 17981ndash17986 2013

[58] G D Geske J C OrsquoNeill D M Miller M E Mattmannand H E Blackwell ldquoModulation of bacterial quorum sensingwith synthetic ligands systematic evaluation of N-acylatedhomoserine lactones in multiple species and new insights intotheir mechanisms of actionrdquo Journal of the American ChemicalSociety vol 129 no 44 pp 13613ndash13625 2007

[59] B K Khajanchi M L Kirtley S M Brackman A KChopra and B A McCormick ldquoImmunomodulatory and pro-tective roles of quorum-sensing signaling molecules N-acylhomoserine lactones during infection of mice with aeromonashydrophilardquo Infection and Immunity vol 79 no 7 pp 2646ndash2657 2011

[60] H Tomioka C Sano and Y Tatano ldquoHost-directed therapeu-tics against mycobacterial infectionsrdquo Current PharmaceuticalDesign vol 23 no 18 pp 2644ndash2656 2017

[61] M R Parsek D L Val B L Hanzelka J E Cronan Jr and EP Greenberg ldquoAcyl homoserine-lactone quorum-sensing signalgenerationrdquo Proceedings of the National Acadamy of Sciences ofthe United States of America vol 96 no 8 pp 4360ndash4365 1999

[62] MK Yadav SW Park SW Chae and J J Song ldquoSinefungin anatural nucleoside analogue of S-adenosylmethionine inhibitsStreptococcus pneumoniae biofilm growthrdquo BioMed ResearchInternational vol 2014 Article ID 156987 10 pages 2014

[63] M Hentzer and M Givskov ldquoPharmacological inhibition ofquorum sensing for the treatment of chronic bacterial infec-tionsrdquo The Journal of Clinical Investigation vol 112 no 9 pp1300ndash1307 2003

[64] V Singh G B Evans D H Lenz et al ldquoFemtomolar tran-sition state analogue inhibitors of 5rsquo-methylthioadenosineS-adenosylhomocysteine nucleosidase fromEscherichia colirdquoTheJournal of Biological Chemistry vol 280 no 18 pp 18265ndash182732005

[65] A Priyadarshi E E Kim and K Y Hwang ldquo Structuralinsights into Staphylococcus aureus enoyl-ACP reductase (FabI)

BioMed Research International 13

in complex with NADP and triclosan rdquo Proteins StructureFunction and Bioinformatics vol 78 no 2 pp 480ndash486 2010

[66] N Surolia and A Surolia ldquoTriclosan offers protection againstblood stages of malaria by inhibiting enoyl-ACP reductase ofPlasmodium falciparumrdquoNatureMedicine vol 7 no 2 pp 167ndash173 2001

[67] E Krol and A Becker ldquoRhizobial homologs of the fattyacid transporter FadL facilitate perception of long-chainacyl-homoserine lactone signalsrdquo Proceedings of the NationalAcadamy of Sciences of the United States of America vol 111 no29 pp 10702ndash10707 2014

[68] J L Copitch R N Whitehead and M A Webber ldquoPrevalenceof decreased susceptibility to triclosan in Salmonella entericaisolates fromanimals andhumans andassociationwithmultipledrug resistancerdquo International Journal of Antimicrobial Agentsvol 36 no 3 pp 247ndash251 2010

[69] S Lu N Wang S Ma X Hu L Kang and Y Yu ldquoParabensand triclosan in shellfish fromShenzhen coastal waters bioindi-cation of pollution and human health risksrdquo EnvironmentalPollution vol 246 pp 257ndash263 2018

[70] N Huma P Shankar J Kushwah et al ldquoDiversity and poly-morphism in AHL-Lactonase gene (aiiA) of Bacillusrdquo Journalof Microbiology and Biotechnology vol 21 no 10 pp 1001ndash10112011

[71] S Y Park B J Hwang M Shin J Kim H Kim and J LeeldquoN-acylhomoserine lactonase-producingRhodococcussppwithdifferent AHL-degrading activitiesrdquo FEMSMicrobiology Lettersvol 261 no 1 pp 102ndash108 2006

[72] A Guendouze L Plener J Bzdrenga et al ldquoEffect of quo-rum quenching lactonase in clinical isolates of pseudomonasaeruginosa and comparison with quorum sensing inhibitorsrdquoFrontiers in Microbiology vol 8 p 227 2017

[73] S Hraiech J Hiblot J Lafleur et al ldquoInhaled lactonase reducespseudomonas aeruginosa quorum sensing and mortality in ratpneumoniardquo PLoS ONE vol 9 no 10 Article ID e107125 2014

[74] J Y Chow Y Yang S B Tay K L Chua and W S YewldquoDisruption of biofilm formation by the human pathogenacinetobacter baumannii using engineered quorum-quenchinglactonasesrdquoAntimicrobial Agents andChemotherapy vol 58 no3 pp 1802ndash1805 2014

[75] X FanM Liang L Wang R Chen H Li and X Liu ldquoAii810 anovel cold-adapted N-acylhomoserine lactonase discovered inametagenome can strongly attenuate Pseudomonas aeruginosavirulence factors and biofilm formationrdquo Frontiers in Microbiol-ogy vol 8 p 1950 2017

[76] MM Sakr KM AboshanabW F ElkhatibMA Yassien andN AHassouna ldquoOverexpressed recombinant quorumquench-ing lactonase reduces the virulence motility and biofilm for-mationofmultidrug-resistant Pseudomonas aeruginosa clinicalisolatesrdquo Appl Microbiol Biotechnol vol 102 no 24 pp 10613ndash10622 2018

[77] C Schipper C Hornung P Bijtenhoorn M Quitschau SGrond andW R Streit ldquoMetagenome-derived clones encodingtwo novel lactonase family proteins involved in biofilm inhibi-tion in pseudomonas aeruginosardquo Applied and EnvironmentalMicrobiology vol 75 no 1 pp 224ndash233 2008

[78] W Dong J Zhu X Guo et al ldquoCharacterization of AiiKan AHL lactonase from Kurthia huakui LAM0618T and itsapplication in quorum quenching on Pseudomonas aeruginosaPAO1rdquo Scientific Reports vol 8 no 1 p 6013 2018

[79] W Liu C Ran Z Liu et al ldquoEffects of dietary Lactobacillusplantarum and AHL lactonase on the control of Aeromonas

hydrophila infection in tilapiardquoMicrobiologyopen vol 5 no 4pp 687ndash699 2016

[80] M Torres J C Reina J C Fuentes-Monteverde et al ldquoAHL-lactonase expression in three marine emerging pathogenicVibrio spp reduces virulence and mortality in brine shrimp(Artemia salina) and Manila clam (Venerupis philippinarum)rdquoPLoS ONE vol 13 no 4 Article ID e0195176 2018

[81] G Vinoj B Vaseeharan S Thomas A J Spiers and S ShanthildquoQuorum-quenching activity of the AHL-lactonase from bacil-lus licheniformis DAHB1 inhibits vibrio biofilm formation invitro and reduces shrimp intestinal colonisation andmortalityrdquoMarine Biotechnology vol 16 no 6 pp 707ndash715 2014

[82] V C Kalia ldquoIn search of versatile organisms for quorum-sensing inhibitors acyl homoserine lactones (AHL)-acylaseand AHL-lactonaserdquo FEMS Microbiology Letters vol 359 no2 p 143 2014

[83] V B Maisuria and A S Nerurkar ldquoInterference of quorumsensing by Delftia sp VM4 depends on the activity of a noveln-acylhomoserine lactone-acylaserdquo PLoS ONE vol 10 no 9Article ID e0138034 2015

[84] R Mukherji N K Varshney P Panigrahi C Suresh and APrabhune ldquoA new role for penicillin acylases degradation ofacyl homoserine lactone quorum sensing signals by Kluyveracitrophila penicillin G acylaserdquo Enzyme and Microbial Technol-ogy vol 56 pp 1ndash7 2014

[85] C F Sio L G Otten R H Cool et al ldquoQuorum quenchingby an N-acyl-homoserine lactone acylase from Pseudomonasaeruginosa PAO1rdquo Infection and Immunity vol 74 no 3 pp1673ndash1682 2006

[86] K Ivanova M M Fernandes E Mendoza and T TzanovldquoEnzyme multilayer coatings inhibit Pseudomonas aeruginosabiofilm formation on urinary cathetersrdquo Applied Microbiologyand Biotechnology vol 99 no 10 pp 4373ndash4385 2015

[87] N Grover J G Plaks S R Summers G R Chado M J Schurrand J L Kaar ldquoAcylase-containing polyurethane coatings withanti-biofilm activityrdquo Biotechnology and Bioengineering vol 113no 12 pp 2535ndash2543 2016

[88] J Lee I Lee J Nam D S Hwang K-M Yeon and JKim ldquoImmobilization and stabilization of acylase on carboxy-lated polyaniline nanofibers for highly effective antifoulingapplication via quorum quenchingrdquo ACS Applied Materials ampInterfaces vol 9 no 18 pp 15424ndash15432 2017

[89] S Uroz S R Chhabra M Camara P Williams P Ogerand Y Dessaux ldquoN-acylhomoserine lactone quorum-sensingmolecules are modified and degraded by Rhodococcus ery-thropolis W2 by both amidolytic and novel oxidoreductaseactivitiesrdquoMicrobiology vol 151 no 10 pp 3313ndash3322 2005

[90] B Eva and S Maria ldquoMicrobial secondary metabolites asinhibitors of pharmaceutically important transferases and oxi-doreductasesrdquo Ceska Slov Farm vol 61 no 3 pp 107ndash114 2012

[91] P Bijtenhoorn H Mayerhofer J Muller-Dieckmann et alldquoA novel metagenomic Short-Chain dehydrogenasereductaseattenuates pseudomonas Aeruginosa biofilm formation andvirulence on Caenorhabditis elegansrdquo PLoS ONE vol 6 no 10Article ID e26278 2011

[92] J D Wildschut R M Lang J K Voordouw and G Voor-douw ldquoRubredoxin oxygen oxidoreductase enhances survivalof desulfovibrio vulgaris hildenborough under microaerophilicconditionsrdquo Journal of Bacteriology vol 188 no 17 pp 6253ndash6260 2006

14 BioMed Research International

[93] X Zhang S Ou-yang JWang L Liao RWu and JWei ldquoCon-struction of antibacterial surface via layer-by-layer methodrdquoCurrent Pharmaceutical Design vol 24 no 8 pp 926ndash935 2018

[94] C Pustelny A Albers K Buldt-Karentzopoulos et al ldquoDiox-ygenase-mediated quenching of quinolone-dependent quorumsensing in pseudomonas aeruginosardquoChemistry amp Biology vol16 no 12 pp 1259ndash1267 2009

[95] J T Hodgkinson W R Galloway M Welch and DR Spring ldquoMicrowave-assisted preparation of the quorum-sensing molecule 2-heptyl-3-hydroxy-4(1H)-quinolone andstructurally related analogsrdquo Nature Protocols vol 7 no 6 pp1184ndash1192 2012

[96] F Witzgall T Depke M Hoffmann et al ldquoThe alkylquinolonerepertoire of Pseudomonas aeruginosa is linked to structuralflexibility of the fabh-like 2-heptyl-3-hydroxy-4(1H)-quinolone(PQS) biosynthesis enzyme PqsBCrdquo ChemBioChem vol 19 no14 pp 1531ndash1544 2018

[97] L Andresen E Sala V Koiv and A Mae ldquoA role for theRcs phosphorelay in regulating expression of plant cell walldegrading enzymes in Pectobacterium carotovorum subspcarotovorumrdquoMicrobiology vol 156 no 5 pp 1323ndash1334 2010

[98] L Andresen V Koiv T Alamae and A Mae ldquoThe Rcs phos-phorelay modulates the expression of plant cell wall degradingenzymes and virulence in Pectobacterium carotovorum sspcarotovorumrdquo FEMS Microbiology Letters vol 273 no 2 pp229ndash238 2007

[99] R K Gupta S Chhibber and K Harjai ldquoAcyl homoserinelactones from culture supernatants of pseudomonas aeruginosaaccelerate host immunomodulationrdquo PLoS ONE vol 6 no 6Article ID e20860 2011

[100] G F Kaufmann J Park J M Mee R J Ulevitch and KD Janda ldquoThe quorum quenching antibody RS2-1G9 protectsmacrophages from the cytotoxic effects of the Pseudomonasaeruginosa quorum sensing signalling molecule N-3-oxo-dodecanoyl-homoserine lactonerdquo Molecular Immunology vol45 no 9 pp 2710ndash2714 2008

[101] S Koul J Prakash A Mishra and V C Kalia ldquoPotential emer-gence of multi-quorum sensing inhibitor resistant (MQSIR)bacteriardquo Indian Journal of Microbiology vol 56 no 1 pp 1ndash182016

[102] T Praneenararat A G Palmer and H E Blackwell ldquoChemicalmethods to interrogate bacterial quorum sensing pathwaysrdquoOrganicampBiomolecular Chemistry vol 10 no 41 pp 8189ndash81992012

[103] J Park R Jagasia G F Kaufmann et al ldquoInfection controlby antibody disruption of bacterial quorum sensing signalingrdquoChemistry amp Biology vol 14 no 10 pp 1119ndash1127 2007

[104] C Grandclement M Tannieres S Morera Y Dessaux DFaure andM Camara ldquoQuorum quenching role in nature andapplied developmentsrdquo FEMSMicrobiology Reviews vol 40 no1 pp 86ndash116 2016

[105] MHan J GuG F Gao andW J Liu ldquoChina in action nationalstrategies to combat against emerging infectious diseasesrdquoScience China Life Sciences vol 60 no 12 pp 1383ndash1385 2017

[106] J Liu H Yu Y Huang et al ldquoComplete genome sequence ofa novel bacteriophage infecting Bradyrhizobium diazoefficiensUSDA110rdquo Science China Life Sciences vol 61 no 1 pp 118ndash1212018

[107] L D Christensen M van Gennip T H Jakobsen et alldquoSynergistic antibacterial efficacy of early combination treat-ment with tobramycin and quorum-sensing inhibitors against

Pseudomonas aeruginosa in an intraperitoneal foreign-bodyinfection mouse modelrdquo Journal of Antimicrobial Chemother-apy vol 67 no 5 pp 1198ndash1206 2012

[108] J Fong M Yuan T H Jakobsen et al ldquoDisulfide bond-containing ajoene analogues as novel quorum sensinginhibitors of Pseudomonas aeruginosardquo Journal of MedicinalChemistry vol 60 no 1 pp 215ndash227 2017

[109] R Garcıa-Contreras M Martınez-Vazquez N VelazquezGuadarrama et al ldquo Resistance to the quorum-quenchingcompounds brominated furanone C-30 and 5-fluorouracil inPseudomonas aeruginosa clinical isolates rdquo Pathogens and Dis-ease vol 68 no 1 pp 8ndash11 2013

[110] T H Jakobsen S K Bragason R K Phipps et al ldquoFood as asource for quorum sensing inhibitors iberin from horseradishrevealed as a quorum sensing inhibitor of pseudomonas aerug-inosardquo Applied and Environmental Microbiology vol 78 no 7pp 2410ndash2421 2012

[111] A Vadekeetil H Saini S Chhibber and K Harjai ldquo Exploitingthe antivirulence efficacy of an ajoene-ciprofloxacin combina-tion against Pseudomonas aeruginosa biofilm associatedmurineacute pyelonephritis rdquo Biofouling vol 32 no 4 pp 371ndash3822016

[112] S Bahari H Zeighami H Mirshahabi S Roudashti and FHaghi ldquoInhibition of pseudomonas aeruginosa quorum sensingby subinhibitory concentrations of curcumin with gentamicinand azithromycinrdquo Journal of Global Antimicrobial Resistancevol 10 pp 21ndash28 2017

[113] A S Roccaro A R Blanco F Giuliano D Rusciano and VEnea ldquoEpigallocatechin-gallate enhances the activity of tetra-cycline in staphylococci by inhibiting its efflux from bacterialcellsrdquo Antimicrobial Agents and Chemotherapy vol 48 no 6pp 1968ndash1973 2004

[114] C Chu J Deng Y Man and Y Qu ldquoGreen tea extractsepigallocatechin-3-gallate for different treatmentsrdquo BioMedResearch International vol 2017 Article ID 5615647 9 pages2017

[115] A Furiga B Lajoie S El Hage G Baziard and C RoquesldquoImpairment of pseudomonas aeruginosa biofilm resistance toantibiotics by combining the drugs with a new quorum-sensinginhibitorrdquo Antimicrobial Agents and Chemotherapy vol 60 no3 pp 1676ndash1686 2016

[116] Y Inoue N Togashi and H Hamashima ldquoFarnesol-induceddisruption of the staphylococcus aureus cytoplasmic mem-branerdquo Biological and Pharmaceutical Bulletin vol 39 no 5 pp653ndash656 2016

[117] C Kim D Hesek M Lee and S Mobashery ldquoPotentiationof the activity of beta-lactam antibiotics by farnesol and itsderivativesrdquo Bioorganic amp Medicinal Chemistry Letters vol 28no 4 pp 642ndash645 2018

[118] G Brackman P Cos L Maes H J Nelis and T Coenye ldquoQuo-rum sensing inhibitors increase the susceptibility of bacterialbiofilms to antibiotics in vitro and in vivordquoAntimicrobial Agentsand Chemotherapy vol 55 no 6 pp 2655ndash2661 2011

[119] G Brackman K Breyne R De Rycke et al ldquoThe quorum sens-ing inhibitor hamamelitannin increases antibiotic susceptibilityof staphylococcus aureus biofilms by affecting peptidoglycanbiosynthesis and eDNA releaserdquo Scientific Reports vol 6 ArticleID 20321 2016

[120] J M Walz R L Avelar K J Longtine K L Carter L A Mer-mel and S O Heard ldquoAnti-infective external coating of centralvenous catheters A randomized noninferiority trial comparing

BioMed Research International 15

5-fluorouracil with chlorhexidinesilver sulfadiazine in pre-venting catheter colonizationrdquo Critical Care Medicine vol 38no 11 pp 2095ndash2102 2010

[121] C van Delden T Kohler F Brunner-Ferber B Francois JCarlet and J Pechere ldquoAzithromycin to prevent Pseudomonasaeruginosa ventilator-associated pneumonia by inhibition ofquorum sensing a randomized controlled trialrdquo Intensive CareMedicine vol 38 no 7 pp 1118ndash1125 2012

[122] A R Smyth P M Cifelli C A Ortori et al ldquoGarlic asan inhibitor of Pseudomonas aeruginosa quorum sensing incystic fibrosisndasha pilot randomized controlled trialrdquo PediatricPulmonology vol 45 no 4 pp 356ndash362 2010

Hindawiwwwhindawicom

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Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

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Hindawiwwwhindawicom Volume 2018

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Nucleic AcidsJournal of

Volume 2018

Submit your manuscripts atwwwhindawicom

12 BioMed Research International

concentration in evaluation of antibiotic sensitivity of entero-cocci causing peritonitisrdquo Peritoneal Dialysis International vol27 no 4 pp 464-465 2007

[39] B A Niemira and E B Solomon ldquoSensitivity of planktonicand biofilm-associated salmonella spp to ionizing radiationrdquoApplied andEnvironmentalMicrobiology vol 71 no 5 pp 2732ndash2736 2005

[40] A M Gamage G Shui M R Wenk and K L Chua ldquoN-Octanoylhomoserine lactone signalling mediated by the BpsI-BpsR quorum sensing system plays a major role in biofilmformationofBurkholderia pseudomalleirdquoMicrobiology vol 157no 4 pp 1176ndash1186 2011

[41] S H Hong M Hegde J Kim X Wang A Jayaraman andT K Wood ldquoSynthetic quorum-sensing circuit to controlconsortial biofilm formation and dispersal in a microfluidicdevicerdquo Nature Communications vol 3 p 613 2012

[42] P Sankar Ganesh and V Ravishankar Rai ldquoAttenuation ofquorum-sensing-dependent virulence factors and biofilm for-mation by medicinal plants against antibiotic resistant Pseu-domonas aeruginosardquo Journal of Traditional and Complemen-tary Medicine vol 8 no 1 pp 170ndash177 2018

[43] P Shih ldquoEffects of quorum-sensing deficiency on Pseudomonasaeruginosa biofilm formation and antibiotic resistancerdquo Journalof Antimicrobial Chemotherapy vol 49 no 2 pp 309ndash314

[44] M I Chernukha I A Shaginian IM Romanova G VMaleevand A L Gintsburg ldquoThe role of ldquoquorum sensingrdquo regula-tion system in symbiotic interaction of bacteria Burkholderiacepacia and Pseudomonas aeruginosa during mixed infectionrdquoZhurnalMikrobiologii Epidemiologii Immunobiologii no 4 pp32ndash37 2006

[45] F M Husain I Ahmad A S Al-Thubiani H H AbulreeshI M AlHazza and F Aqil ldquoLeaf extracts of Mangifera indicaL inhibit quorum sensing - Regulated production of virulencefactors and biofilm in test bacteriardquo Frontiers in Microbiologyvol 8 p 727 2017

[46] D G Renter J G Morris J M Sargeant et al ldquoPreva-lence risk factors O serogroups and virulence profiles ofshiga toxinndashproducing bacteria from cattle production environ-mentsrdquo Journal of Food Protection vol 68 no 8 pp 1556ndash15652005

[47] A R Hauser ldquoPseudomonas aeruginosa So many virulencefactors so little timerdquo Critical Care Medicine vol 39 no 9 pp2193-2194 2011

[48] R Le Berre S Nguyen E Nowak et al ldquoRelative contributionof three main virulence factors in Pseudomonas aeruginosapneumoniardquo Critical Care Medicine vol 39 no 9 pp 2113ndash2120 2011

[49] M M Gallardo-Garcia G Sanchez-Espin R Ivanova-Georgieva et al ldquoRelationship between pathogenic clinicaland virulence factors of Staphylococcus aureus in infectiveendocarditis versus uncomplicated bacteremia a case-controlstudyrdquo European Journal of Clinical Microbiology amp InfectiousDiseases vol 35 no 5 pp 821ndash828 2016

[50] F Sabouni S Mahmoudi A Bahador et al ldquoVirulence factorsof staphylococcus aureus isolates in an iranian referral childrenrsquoshospitalrdquo Osong Public Health and Research Perspectives vol 5no 2 pp 96ndash100 2014

[51] H M Aboushleib H M Omar R Abozahra A Elsheredyand K Baraka ldquoCorrelation of quorum sensing and virulencefactors in Pseudomonas aeruginosa isolates in Egyptrdquo TheJournal of Infection in Developing Countries vol 9 no 10 pp1091ndash1099 2015

[52] R T Sturbelle L F Avila T B Roos et al ldquoThe role ofquorum sensing in Escherichia coli (ETEC) virulence factorsrdquoVeterinary Microbiology vol 180 no 3-4 pp 245ndash252 2015

[53] J E Paczkowski S Mukherjee A R McCready et alldquoFlavonoids suppress Pseudomonas aeruginosa Virulencethrough allosteric inhibition of quorum-sensing receptorsrdquoTheJournal of Biological Chemistry vol 292 no 10 pp 4064ndash40762017

[54] L Weng Y Yang Y Zhang and L Wang ldquoA new syntheticligand that activatesQscRand blocks antibiotic-tolerant biofilmformation in Pseudomonas aeruginosardquo Applied Microbiologyand Biotechnology vol 98 no 6 pp 2565ndash2572 2014

[55] Y-X Yang Z-H Xu Y-Q Zhang J Tian L-X Wengand L-H Wang ldquoA new quorum-sensing inhibitor attenuatesvirulence and decreases antibiotic resistance in Pseudomonasaeruginosardquo Journal of Microbiology vol 50 no 6 pp 987ndash9932012

[56] J N Capilato S V Philippi T Reardon et al ldquoDevelopment ofa novel series of non-natural triaryl agonists and antagonists ofthe Pseudomonas aeruginosa LasR quorum sensing receptorrdquoBioorganic amp Medicinal Chemistry vol 25 no 1 pp 153ndash1652017

[57] C T OrsquoLoughlin L C Miller A Siryaporn K Drescher MF Semmelhack and B L Bassler ldquoA quorum-sensing inhibitorblocks Pseudomonas aeruginosa virulence and biofilm forma-tionrdquo Proceedings of the National Acadamy of Sciences of theUnited States of America vol 110 no 44 pp 17981ndash17986 2013

[58] G D Geske J C OrsquoNeill D M Miller M E Mattmannand H E Blackwell ldquoModulation of bacterial quorum sensingwith synthetic ligands systematic evaluation of N-acylatedhomoserine lactones in multiple species and new insights intotheir mechanisms of actionrdquo Journal of the American ChemicalSociety vol 129 no 44 pp 13613ndash13625 2007

[59] B K Khajanchi M L Kirtley S M Brackman A KChopra and B A McCormick ldquoImmunomodulatory and pro-tective roles of quorum-sensing signaling molecules N-acylhomoserine lactones during infection of mice with aeromonashydrophilardquo Infection and Immunity vol 79 no 7 pp 2646ndash2657 2011

[60] H Tomioka C Sano and Y Tatano ldquoHost-directed therapeu-tics against mycobacterial infectionsrdquo Current PharmaceuticalDesign vol 23 no 18 pp 2644ndash2656 2017

[61] M R Parsek D L Val B L Hanzelka J E Cronan Jr and EP Greenberg ldquoAcyl homoserine-lactone quorum-sensing signalgenerationrdquo Proceedings of the National Acadamy of Sciences ofthe United States of America vol 96 no 8 pp 4360ndash4365 1999

[62] MK Yadav SW Park SW Chae and J J Song ldquoSinefungin anatural nucleoside analogue of S-adenosylmethionine inhibitsStreptococcus pneumoniae biofilm growthrdquo BioMed ResearchInternational vol 2014 Article ID 156987 10 pages 2014

[63] M Hentzer and M Givskov ldquoPharmacological inhibition ofquorum sensing for the treatment of chronic bacterial infec-tionsrdquo The Journal of Clinical Investigation vol 112 no 9 pp1300ndash1307 2003

[64] V Singh G B Evans D H Lenz et al ldquoFemtomolar tran-sition state analogue inhibitors of 5rsquo-methylthioadenosineS-adenosylhomocysteine nucleosidase fromEscherichia colirdquoTheJournal of Biological Chemistry vol 280 no 18 pp 18265ndash182732005

[65] A Priyadarshi E E Kim and K Y Hwang ldquo Structuralinsights into Staphylococcus aureus enoyl-ACP reductase (FabI)

BioMed Research International 13

in complex with NADP and triclosan rdquo Proteins StructureFunction and Bioinformatics vol 78 no 2 pp 480ndash486 2010

[66] N Surolia and A Surolia ldquoTriclosan offers protection againstblood stages of malaria by inhibiting enoyl-ACP reductase ofPlasmodium falciparumrdquoNatureMedicine vol 7 no 2 pp 167ndash173 2001

[67] E Krol and A Becker ldquoRhizobial homologs of the fattyacid transporter FadL facilitate perception of long-chainacyl-homoserine lactone signalsrdquo Proceedings of the NationalAcadamy of Sciences of the United States of America vol 111 no29 pp 10702ndash10707 2014

[68] J L Copitch R N Whitehead and M A Webber ldquoPrevalenceof decreased susceptibility to triclosan in Salmonella entericaisolates fromanimals andhumans andassociationwithmultipledrug resistancerdquo International Journal of Antimicrobial Agentsvol 36 no 3 pp 247ndash251 2010

[69] S Lu N Wang S Ma X Hu L Kang and Y Yu ldquoParabensand triclosan in shellfish fromShenzhen coastal waters bioindi-cation of pollution and human health risksrdquo EnvironmentalPollution vol 246 pp 257ndash263 2018

[70] N Huma P Shankar J Kushwah et al ldquoDiversity and poly-morphism in AHL-Lactonase gene (aiiA) of Bacillusrdquo Journalof Microbiology and Biotechnology vol 21 no 10 pp 1001ndash10112011

[71] S Y Park B J Hwang M Shin J Kim H Kim and J LeeldquoN-acylhomoserine lactonase-producingRhodococcussppwithdifferent AHL-degrading activitiesrdquo FEMSMicrobiology Lettersvol 261 no 1 pp 102ndash108 2006

[72] A Guendouze L Plener J Bzdrenga et al ldquoEffect of quo-rum quenching lactonase in clinical isolates of pseudomonasaeruginosa and comparison with quorum sensing inhibitorsrdquoFrontiers in Microbiology vol 8 p 227 2017

[73] S Hraiech J Hiblot J Lafleur et al ldquoInhaled lactonase reducespseudomonas aeruginosa quorum sensing and mortality in ratpneumoniardquo PLoS ONE vol 9 no 10 Article ID e107125 2014

[74] J Y Chow Y Yang S B Tay K L Chua and W S YewldquoDisruption of biofilm formation by the human pathogenacinetobacter baumannii using engineered quorum-quenchinglactonasesrdquoAntimicrobial Agents andChemotherapy vol 58 no3 pp 1802ndash1805 2014

[75] X FanM Liang L Wang R Chen H Li and X Liu ldquoAii810 anovel cold-adapted N-acylhomoserine lactonase discovered inametagenome can strongly attenuate Pseudomonas aeruginosavirulence factors and biofilm formationrdquo Frontiers in Microbiol-ogy vol 8 p 1950 2017

[76] MM Sakr KM AboshanabW F ElkhatibMA Yassien andN AHassouna ldquoOverexpressed recombinant quorumquench-ing lactonase reduces the virulence motility and biofilm for-mationofmultidrug-resistant Pseudomonas aeruginosa clinicalisolatesrdquo Appl Microbiol Biotechnol vol 102 no 24 pp 10613ndash10622 2018

[77] C Schipper C Hornung P Bijtenhoorn M Quitschau SGrond andW R Streit ldquoMetagenome-derived clones encodingtwo novel lactonase family proteins involved in biofilm inhibi-tion in pseudomonas aeruginosardquo Applied and EnvironmentalMicrobiology vol 75 no 1 pp 224ndash233 2008

[78] W Dong J Zhu X Guo et al ldquoCharacterization of AiiKan AHL lactonase from Kurthia huakui LAM0618T and itsapplication in quorum quenching on Pseudomonas aeruginosaPAO1rdquo Scientific Reports vol 8 no 1 p 6013 2018

[79] W Liu C Ran Z Liu et al ldquoEffects of dietary Lactobacillusplantarum and AHL lactonase on the control of Aeromonas

hydrophila infection in tilapiardquoMicrobiologyopen vol 5 no 4pp 687ndash699 2016

[80] M Torres J C Reina J C Fuentes-Monteverde et al ldquoAHL-lactonase expression in three marine emerging pathogenicVibrio spp reduces virulence and mortality in brine shrimp(Artemia salina) and Manila clam (Venerupis philippinarum)rdquoPLoS ONE vol 13 no 4 Article ID e0195176 2018

[81] G Vinoj B Vaseeharan S Thomas A J Spiers and S ShanthildquoQuorum-quenching activity of the AHL-lactonase from bacil-lus licheniformis DAHB1 inhibits vibrio biofilm formation invitro and reduces shrimp intestinal colonisation andmortalityrdquoMarine Biotechnology vol 16 no 6 pp 707ndash715 2014

[82] V C Kalia ldquoIn search of versatile organisms for quorum-sensing inhibitors acyl homoserine lactones (AHL)-acylaseand AHL-lactonaserdquo FEMS Microbiology Letters vol 359 no2 p 143 2014

[83] V B Maisuria and A S Nerurkar ldquoInterference of quorumsensing by Delftia sp VM4 depends on the activity of a noveln-acylhomoserine lactone-acylaserdquo PLoS ONE vol 10 no 9Article ID e0138034 2015

[84] R Mukherji N K Varshney P Panigrahi C Suresh and APrabhune ldquoA new role for penicillin acylases degradation ofacyl homoserine lactone quorum sensing signals by Kluyveracitrophila penicillin G acylaserdquo Enzyme and Microbial Technol-ogy vol 56 pp 1ndash7 2014

[85] C F Sio L G Otten R H Cool et al ldquoQuorum quenchingby an N-acyl-homoserine lactone acylase from Pseudomonasaeruginosa PAO1rdquo Infection and Immunity vol 74 no 3 pp1673ndash1682 2006

[86] K Ivanova M M Fernandes E Mendoza and T TzanovldquoEnzyme multilayer coatings inhibit Pseudomonas aeruginosabiofilm formation on urinary cathetersrdquo Applied Microbiologyand Biotechnology vol 99 no 10 pp 4373ndash4385 2015

[87] N Grover J G Plaks S R Summers G R Chado M J Schurrand J L Kaar ldquoAcylase-containing polyurethane coatings withanti-biofilm activityrdquo Biotechnology and Bioengineering vol 113no 12 pp 2535ndash2543 2016

[88] J Lee I Lee J Nam D S Hwang K-M Yeon and JKim ldquoImmobilization and stabilization of acylase on carboxy-lated polyaniline nanofibers for highly effective antifoulingapplication via quorum quenchingrdquo ACS Applied Materials ampInterfaces vol 9 no 18 pp 15424ndash15432 2017

[89] S Uroz S R Chhabra M Camara P Williams P Ogerand Y Dessaux ldquoN-acylhomoserine lactone quorum-sensingmolecules are modified and degraded by Rhodococcus ery-thropolis W2 by both amidolytic and novel oxidoreductaseactivitiesrdquoMicrobiology vol 151 no 10 pp 3313ndash3322 2005

[90] B Eva and S Maria ldquoMicrobial secondary metabolites asinhibitors of pharmaceutically important transferases and oxi-doreductasesrdquo Ceska Slov Farm vol 61 no 3 pp 107ndash114 2012

[91] P Bijtenhoorn H Mayerhofer J Muller-Dieckmann et alldquoA novel metagenomic Short-Chain dehydrogenasereductaseattenuates pseudomonas Aeruginosa biofilm formation andvirulence on Caenorhabditis elegansrdquo PLoS ONE vol 6 no 10Article ID e26278 2011

[92] J D Wildschut R M Lang J K Voordouw and G Voor-douw ldquoRubredoxin oxygen oxidoreductase enhances survivalof desulfovibrio vulgaris hildenborough under microaerophilicconditionsrdquo Journal of Bacteriology vol 188 no 17 pp 6253ndash6260 2006

14 BioMed Research International

[93] X Zhang S Ou-yang JWang L Liao RWu and JWei ldquoCon-struction of antibacterial surface via layer-by-layer methodrdquoCurrent Pharmaceutical Design vol 24 no 8 pp 926ndash935 2018

[94] C Pustelny A Albers K Buldt-Karentzopoulos et al ldquoDiox-ygenase-mediated quenching of quinolone-dependent quorumsensing in pseudomonas aeruginosardquoChemistry amp Biology vol16 no 12 pp 1259ndash1267 2009

[95] J T Hodgkinson W R Galloway M Welch and DR Spring ldquoMicrowave-assisted preparation of the quorum-sensing molecule 2-heptyl-3-hydroxy-4(1H)-quinolone andstructurally related analogsrdquo Nature Protocols vol 7 no 6 pp1184ndash1192 2012

[96] F Witzgall T Depke M Hoffmann et al ldquoThe alkylquinolonerepertoire of Pseudomonas aeruginosa is linked to structuralflexibility of the fabh-like 2-heptyl-3-hydroxy-4(1H)-quinolone(PQS) biosynthesis enzyme PqsBCrdquo ChemBioChem vol 19 no14 pp 1531ndash1544 2018

[97] L Andresen E Sala V Koiv and A Mae ldquoA role for theRcs phosphorelay in regulating expression of plant cell walldegrading enzymes in Pectobacterium carotovorum subspcarotovorumrdquoMicrobiology vol 156 no 5 pp 1323ndash1334 2010

[98] L Andresen V Koiv T Alamae and A Mae ldquoThe Rcs phos-phorelay modulates the expression of plant cell wall degradingenzymes and virulence in Pectobacterium carotovorum sspcarotovorumrdquo FEMS Microbiology Letters vol 273 no 2 pp229ndash238 2007

[99] R K Gupta S Chhibber and K Harjai ldquoAcyl homoserinelactones from culture supernatants of pseudomonas aeruginosaaccelerate host immunomodulationrdquo PLoS ONE vol 6 no 6Article ID e20860 2011

[100] G F Kaufmann J Park J M Mee R J Ulevitch and KD Janda ldquoThe quorum quenching antibody RS2-1G9 protectsmacrophages from the cytotoxic effects of the Pseudomonasaeruginosa quorum sensing signalling molecule N-3-oxo-dodecanoyl-homoserine lactonerdquo Molecular Immunology vol45 no 9 pp 2710ndash2714 2008

[101] S Koul J Prakash A Mishra and V C Kalia ldquoPotential emer-gence of multi-quorum sensing inhibitor resistant (MQSIR)bacteriardquo Indian Journal of Microbiology vol 56 no 1 pp 1ndash182016

[102] T Praneenararat A G Palmer and H E Blackwell ldquoChemicalmethods to interrogate bacterial quorum sensing pathwaysrdquoOrganicampBiomolecular Chemistry vol 10 no 41 pp 8189ndash81992012

[103] J Park R Jagasia G F Kaufmann et al ldquoInfection controlby antibody disruption of bacterial quorum sensing signalingrdquoChemistry amp Biology vol 14 no 10 pp 1119ndash1127 2007

[104] C Grandclement M Tannieres S Morera Y Dessaux DFaure andM Camara ldquoQuorum quenching role in nature andapplied developmentsrdquo FEMSMicrobiology Reviews vol 40 no1 pp 86ndash116 2016

[105] MHan J GuG F Gao andW J Liu ldquoChina in action nationalstrategies to combat against emerging infectious diseasesrdquoScience China Life Sciences vol 60 no 12 pp 1383ndash1385 2017

[106] J Liu H Yu Y Huang et al ldquoComplete genome sequence ofa novel bacteriophage infecting Bradyrhizobium diazoefficiensUSDA110rdquo Science China Life Sciences vol 61 no 1 pp 118ndash1212018

[107] L D Christensen M van Gennip T H Jakobsen et alldquoSynergistic antibacterial efficacy of early combination treat-ment with tobramycin and quorum-sensing inhibitors against

Pseudomonas aeruginosa in an intraperitoneal foreign-bodyinfection mouse modelrdquo Journal of Antimicrobial Chemother-apy vol 67 no 5 pp 1198ndash1206 2012

[108] J Fong M Yuan T H Jakobsen et al ldquoDisulfide bond-containing ajoene analogues as novel quorum sensinginhibitors of Pseudomonas aeruginosardquo Journal of MedicinalChemistry vol 60 no 1 pp 215ndash227 2017

[109] R Garcıa-Contreras M Martınez-Vazquez N VelazquezGuadarrama et al ldquo Resistance to the quorum-quenchingcompounds brominated furanone C-30 and 5-fluorouracil inPseudomonas aeruginosa clinical isolates rdquo Pathogens and Dis-ease vol 68 no 1 pp 8ndash11 2013

[110] T H Jakobsen S K Bragason R K Phipps et al ldquoFood as asource for quorum sensing inhibitors iberin from horseradishrevealed as a quorum sensing inhibitor of pseudomonas aerug-inosardquo Applied and Environmental Microbiology vol 78 no 7pp 2410ndash2421 2012

[111] A Vadekeetil H Saini S Chhibber and K Harjai ldquo Exploitingthe antivirulence efficacy of an ajoene-ciprofloxacin combina-tion against Pseudomonas aeruginosa biofilm associatedmurineacute pyelonephritis rdquo Biofouling vol 32 no 4 pp 371ndash3822016

[112] S Bahari H Zeighami H Mirshahabi S Roudashti and FHaghi ldquoInhibition of pseudomonas aeruginosa quorum sensingby subinhibitory concentrations of curcumin with gentamicinand azithromycinrdquo Journal of Global Antimicrobial Resistancevol 10 pp 21ndash28 2017

[113] A S Roccaro A R Blanco F Giuliano D Rusciano and VEnea ldquoEpigallocatechin-gallate enhances the activity of tetra-cycline in staphylococci by inhibiting its efflux from bacterialcellsrdquo Antimicrobial Agents and Chemotherapy vol 48 no 6pp 1968ndash1973 2004

[114] C Chu J Deng Y Man and Y Qu ldquoGreen tea extractsepigallocatechin-3-gallate for different treatmentsrdquo BioMedResearch International vol 2017 Article ID 5615647 9 pages2017

[115] A Furiga B Lajoie S El Hage G Baziard and C RoquesldquoImpairment of pseudomonas aeruginosa biofilm resistance toantibiotics by combining the drugs with a new quorum-sensinginhibitorrdquo Antimicrobial Agents and Chemotherapy vol 60 no3 pp 1676ndash1686 2016

[116] Y Inoue N Togashi and H Hamashima ldquoFarnesol-induceddisruption of the staphylococcus aureus cytoplasmic mem-branerdquo Biological and Pharmaceutical Bulletin vol 39 no 5 pp653ndash656 2016

[117] C Kim D Hesek M Lee and S Mobashery ldquoPotentiationof the activity of beta-lactam antibiotics by farnesol and itsderivativesrdquo Bioorganic amp Medicinal Chemistry Letters vol 28no 4 pp 642ndash645 2018

[118] G Brackman P Cos L Maes H J Nelis and T Coenye ldquoQuo-rum sensing inhibitors increase the susceptibility of bacterialbiofilms to antibiotics in vitro and in vivordquoAntimicrobial Agentsand Chemotherapy vol 55 no 6 pp 2655ndash2661 2011

[119] G Brackman K Breyne R De Rycke et al ldquoThe quorum sens-ing inhibitor hamamelitannin increases antibiotic susceptibilityof staphylococcus aureus biofilms by affecting peptidoglycanbiosynthesis and eDNA releaserdquo Scientific Reports vol 6 ArticleID 20321 2016

[120] J M Walz R L Avelar K J Longtine K L Carter L A Mer-mel and S O Heard ldquoAnti-infective external coating of centralvenous catheters A randomized noninferiority trial comparing

BioMed Research International 15

5-fluorouracil with chlorhexidinesilver sulfadiazine in pre-venting catheter colonizationrdquo Critical Care Medicine vol 38no 11 pp 2095ndash2102 2010

[121] C van Delden T Kohler F Brunner-Ferber B Francois JCarlet and J Pechere ldquoAzithromycin to prevent Pseudomonasaeruginosa ventilator-associated pneumonia by inhibition ofquorum sensing a randomized controlled trialrdquo Intensive CareMedicine vol 38 no 7 pp 1118ndash1125 2012

[122] A R Smyth P M Cifelli C A Ortori et al ldquoGarlic asan inhibitor of Pseudomonas aeruginosa quorum sensing incystic fibrosisndasha pilot randomized controlled trialrdquo PediatricPulmonology vol 45 no 4 pp 356ndash362 2010

Hindawiwwwhindawicom

International Journal of

Volume 2018

Zoology

Hindawiwwwhindawicom Volume 2018

Anatomy Research International

PeptidesInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Journal of Parasitology Research

GenomicsInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

The Scientific World Journal

Volume 2018

Hindawiwwwhindawicom Volume 2018

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Neuroscience Journal

Hindawiwwwhindawicom Volume 2018

BioMed Research International

Cell BiologyInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Biochemistry Research International

ArchaeaHindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Genetics Research International

Hindawiwwwhindawicom Volume 2018

Advances in

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Hindawiwwwhindawicom Volume 2018

International Journal of

MicrobiologyHindawiwwwhindawicom

Nucleic AcidsJournal of

Volume 2018

Submit your manuscripts atwwwhindawicom

BioMed Research International 13

in complex with NADP and triclosan rdquo Proteins StructureFunction and Bioinformatics vol 78 no 2 pp 480ndash486 2010

[66] N Surolia and A Surolia ldquoTriclosan offers protection againstblood stages of malaria by inhibiting enoyl-ACP reductase ofPlasmodium falciparumrdquoNatureMedicine vol 7 no 2 pp 167ndash173 2001

[67] E Krol and A Becker ldquoRhizobial homologs of the fattyacid transporter FadL facilitate perception of long-chainacyl-homoserine lactone signalsrdquo Proceedings of the NationalAcadamy of Sciences of the United States of America vol 111 no29 pp 10702ndash10707 2014

[68] J L Copitch R N Whitehead and M A Webber ldquoPrevalenceof decreased susceptibility to triclosan in Salmonella entericaisolates fromanimals andhumans andassociationwithmultipledrug resistancerdquo International Journal of Antimicrobial Agentsvol 36 no 3 pp 247ndash251 2010

[69] S Lu N Wang S Ma X Hu L Kang and Y Yu ldquoParabensand triclosan in shellfish fromShenzhen coastal waters bioindi-cation of pollution and human health risksrdquo EnvironmentalPollution vol 246 pp 257ndash263 2018

[70] N Huma P Shankar J Kushwah et al ldquoDiversity and poly-morphism in AHL-Lactonase gene (aiiA) of Bacillusrdquo Journalof Microbiology and Biotechnology vol 21 no 10 pp 1001ndash10112011

[71] S Y Park B J Hwang M Shin J Kim H Kim and J LeeldquoN-acylhomoserine lactonase-producingRhodococcussppwithdifferent AHL-degrading activitiesrdquo FEMSMicrobiology Lettersvol 261 no 1 pp 102ndash108 2006

[72] A Guendouze L Plener J Bzdrenga et al ldquoEffect of quo-rum quenching lactonase in clinical isolates of pseudomonasaeruginosa and comparison with quorum sensing inhibitorsrdquoFrontiers in Microbiology vol 8 p 227 2017

[73] S Hraiech J Hiblot J Lafleur et al ldquoInhaled lactonase reducespseudomonas aeruginosa quorum sensing and mortality in ratpneumoniardquo PLoS ONE vol 9 no 10 Article ID e107125 2014

[74] J Y Chow Y Yang S B Tay K L Chua and W S YewldquoDisruption of biofilm formation by the human pathogenacinetobacter baumannii using engineered quorum-quenchinglactonasesrdquoAntimicrobial Agents andChemotherapy vol 58 no3 pp 1802ndash1805 2014

[75] X FanM Liang L Wang R Chen H Li and X Liu ldquoAii810 anovel cold-adapted N-acylhomoserine lactonase discovered inametagenome can strongly attenuate Pseudomonas aeruginosavirulence factors and biofilm formationrdquo Frontiers in Microbiol-ogy vol 8 p 1950 2017

[76] MM Sakr KM AboshanabW F ElkhatibMA Yassien andN AHassouna ldquoOverexpressed recombinant quorumquench-ing lactonase reduces the virulence motility and biofilm for-mationofmultidrug-resistant Pseudomonas aeruginosa clinicalisolatesrdquo Appl Microbiol Biotechnol vol 102 no 24 pp 10613ndash10622 2018

[77] C Schipper C Hornung P Bijtenhoorn M Quitschau SGrond andW R Streit ldquoMetagenome-derived clones encodingtwo novel lactonase family proteins involved in biofilm inhibi-tion in pseudomonas aeruginosardquo Applied and EnvironmentalMicrobiology vol 75 no 1 pp 224ndash233 2008

[78] W Dong J Zhu X Guo et al ldquoCharacterization of AiiKan AHL lactonase from Kurthia huakui LAM0618T and itsapplication in quorum quenching on Pseudomonas aeruginosaPAO1rdquo Scientific Reports vol 8 no 1 p 6013 2018

[79] W Liu C Ran Z Liu et al ldquoEffects of dietary Lactobacillusplantarum and AHL lactonase on the control of Aeromonas

hydrophila infection in tilapiardquoMicrobiologyopen vol 5 no 4pp 687ndash699 2016

[80] M Torres J C Reina J C Fuentes-Monteverde et al ldquoAHL-lactonase expression in three marine emerging pathogenicVibrio spp reduces virulence and mortality in brine shrimp(Artemia salina) and Manila clam (Venerupis philippinarum)rdquoPLoS ONE vol 13 no 4 Article ID e0195176 2018

[81] G Vinoj B Vaseeharan S Thomas A J Spiers and S ShanthildquoQuorum-quenching activity of the AHL-lactonase from bacil-lus licheniformis DAHB1 inhibits vibrio biofilm formation invitro and reduces shrimp intestinal colonisation andmortalityrdquoMarine Biotechnology vol 16 no 6 pp 707ndash715 2014

[82] V C Kalia ldquoIn search of versatile organisms for quorum-sensing inhibitors acyl homoserine lactones (AHL)-acylaseand AHL-lactonaserdquo FEMS Microbiology Letters vol 359 no2 p 143 2014

[83] V B Maisuria and A S Nerurkar ldquoInterference of quorumsensing by Delftia sp VM4 depends on the activity of a noveln-acylhomoserine lactone-acylaserdquo PLoS ONE vol 10 no 9Article ID e0138034 2015

[84] R Mukherji N K Varshney P Panigrahi C Suresh and APrabhune ldquoA new role for penicillin acylases degradation ofacyl homoserine lactone quorum sensing signals by Kluyveracitrophila penicillin G acylaserdquo Enzyme and Microbial Technol-ogy vol 56 pp 1ndash7 2014

[85] C F Sio L G Otten R H Cool et al ldquoQuorum quenchingby an N-acyl-homoserine lactone acylase from Pseudomonasaeruginosa PAO1rdquo Infection and Immunity vol 74 no 3 pp1673ndash1682 2006

[86] K Ivanova M M Fernandes E Mendoza and T TzanovldquoEnzyme multilayer coatings inhibit Pseudomonas aeruginosabiofilm formation on urinary cathetersrdquo Applied Microbiologyand Biotechnology vol 99 no 10 pp 4373ndash4385 2015

[87] N Grover J G Plaks S R Summers G R Chado M J Schurrand J L Kaar ldquoAcylase-containing polyurethane coatings withanti-biofilm activityrdquo Biotechnology and Bioengineering vol 113no 12 pp 2535ndash2543 2016

[88] J Lee I Lee J Nam D S Hwang K-M Yeon and JKim ldquoImmobilization and stabilization of acylase on carboxy-lated polyaniline nanofibers for highly effective antifoulingapplication via quorum quenchingrdquo ACS Applied Materials ampInterfaces vol 9 no 18 pp 15424ndash15432 2017

[89] S Uroz S R Chhabra M Camara P Williams P Ogerand Y Dessaux ldquoN-acylhomoserine lactone quorum-sensingmolecules are modified and degraded by Rhodococcus ery-thropolis W2 by both amidolytic and novel oxidoreductaseactivitiesrdquoMicrobiology vol 151 no 10 pp 3313ndash3322 2005

[90] B Eva and S Maria ldquoMicrobial secondary metabolites asinhibitors of pharmaceutically important transferases and oxi-doreductasesrdquo Ceska Slov Farm vol 61 no 3 pp 107ndash114 2012

[91] P Bijtenhoorn H Mayerhofer J Muller-Dieckmann et alldquoA novel metagenomic Short-Chain dehydrogenasereductaseattenuates pseudomonas Aeruginosa biofilm formation andvirulence on Caenorhabditis elegansrdquo PLoS ONE vol 6 no 10Article ID e26278 2011

[92] J D Wildschut R M Lang J K Voordouw and G Voor-douw ldquoRubredoxin oxygen oxidoreductase enhances survivalof desulfovibrio vulgaris hildenborough under microaerophilicconditionsrdquo Journal of Bacteriology vol 188 no 17 pp 6253ndash6260 2006

14 BioMed Research International

[93] X Zhang S Ou-yang JWang L Liao RWu and JWei ldquoCon-struction of antibacterial surface via layer-by-layer methodrdquoCurrent Pharmaceutical Design vol 24 no 8 pp 926ndash935 2018

[94] C Pustelny A Albers K Buldt-Karentzopoulos et al ldquoDiox-ygenase-mediated quenching of quinolone-dependent quorumsensing in pseudomonas aeruginosardquoChemistry amp Biology vol16 no 12 pp 1259ndash1267 2009

[95] J T Hodgkinson W R Galloway M Welch and DR Spring ldquoMicrowave-assisted preparation of the quorum-sensing molecule 2-heptyl-3-hydroxy-4(1H)-quinolone andstructurally related analogsrdquo Nature Protocols vol 7 no 6 pp1184ndash1192 2012

[96] F Witzgall T Depke M Hoffmann et al ldquoThe alkylquinolonerepertoire of Pseudomonas aeruginosa is linked to structuralflexibility of the fabh-like 2-heptyl-3-hydroxy-4(1H)-quinolone(PQS) biosynthesis enzyme PqsBCrdquo ChemBioChem vol 19 no14 pp 1531ndash1544 2018

[97] L Andresen E Sala V Koiv and A Mae ldquoA role for theRcs phosphorelay in regulating expression of plant cell walldegrading enzymes in Pectobacterium carotovorum subspcarotovorumrdquoMicrobiology vol 156 no 5 pp 1323ndash1334 2010

[98] L Andresen V Koiv T Alamae and A Mae ldquoThe Rcs phos-phorelay modulates the expression of plant cell wall degradingenzymes and virulence in Pectobacterium carotovorum sspcarotovorumrdquo FEMS Microbiology Letters vol 273 no 2 pp229ndash238 2007

[99] R K Gupta S Chhibber and K Harjai ldquoAcyl homoserinelactones from culture supernatants of pseudomonas aeruginosaaccelerate host immunomodulationrdquo PLoS ONE vol 6 no 6Article ID e20860 2011

[100] G F Kaufmann J Park J M Mee R J Ulevitch and KD Janda ldquoThe quorum quenching antibody RS2-1G9 protectsmacrophages from the cytotoxic effects of the Pseudomonasaeruginosa quorum sensing signalling molecule N-3-oxo-dodecanoyl-homoserine lactonerdquo Molecular Immunology vol45 no 9 pp 2710ndash2714 2008

[101] S Koul J Prakash A Mishra and V C Kalia ldquoPotential emer-gence of multi-quorum sensing inhibitor resistant (MQSIR)bacteriardquo Indian Journal of Microbiology vol 56 no 1 pp 1ndash182016

[102] T Praneenararat A G Palmer and H E Blackwell ldquoChemicalmethods to interrogate bacterial quorum sensing pathwaysrdquoOrganicampBiomolecular Chemistry vol 10 no 41 pp 8189ndash81992012

[103] J Park R Jagasia G F Kaufmann et al ldquoInfection controlby antibody disruption of bacterial quorum sensing signalingrdquoChemistry amp Biology vol 14 no 10 pp 1119ndash1127 2007

[104] C Grandclement M Tannieres S Morera Y Dessaux DFaure andM Camara ldquoQuorum quenching role in nature andapplied developmentsrdquo FEMSMicrobiology Reviews vol 40 no1 pp 86ndash116 2016

[105] MHan J GuG F Gao andW J Liu ldquoChina in action nationalstrategies to combat against emerging infectious diseasesrdquoScience China Life Sciences vol 60 no 12 pp 1383ndash1385 2017

[106] J Liu H Yu Y Huang et al ldquoComplete genome sequence ofa novel bacteriophage infecting Bradyrhizobium diazoefficiensUSDA110rdquo Science China Life Sciences vol 61 no 1 pp 118ndash1212018

[107] L D Christensen M van Gennip T H Jakobsen et alldquoSynergistic antibacterial efficacy of early combination treat-ment with tobramycin and quorum-sensing inhibitors against

Pseudomonas aeruginosa in an intraperitoneal foreign-bodyinfection mouse modelrdquo Journal of Antimicrobial Chemother-apy vol 67 no 5 pp 1198ndash1206 2012

[108] J Fong M Yuan T H Jakobsen et al ldquoDisulfide bond-containing ajoene analogues as novel quorum sensinginhibitors of Pseudomonas aeruginosardquo Journal of MedicinalChemistry vol 60 no 1 pp 215ndash227 2017

[109] R Garcıa-Contreras M Martınez-Vazquez N VelazquezGuadarrama et al ldquo Resistance to the quorum-quenchingcompounds brominated furanone C-30 and 5-fluorouracil inPseudomonas aeruginosa clinical isolates rdquo Pathogens and Dis-ease vol 68 no 1 pp 8ndash11 2013

[110] T H Jakobsen S K Bragason R K Phipps et al ldquoFood as asource for quorum sensing inhibitors iberin from horseradishrevealed as a quorum sensing inhibitor of pseudomonas aerug-inosardquo Applied and Environmental Microbiology vol 78 no 7pp 2410ndash2421 2012

[111] A Vadekeetil H Saini S Chhibber and K Harjai ldquo Exploitingthe antivirulence efficacy of an ajoene-ciprofloxacin combina-tion against Pseudomonas aeruginosa biofilm associatedmurineacute pyelonephritis rdquo Biofouling vol 32 no 4 pp 371ndash3822016

[112] S Bahari H Zeighami H Mirshahabi S Roudashti and FHaghi ldquoInhibition of pseudomonas aeruginosa quorum sensingby subinhibitory concentrations of curcumin with gentamicinand azithromycinrdquo Journal of Global Antimicrobial Resistancevol 10 pp 21ndash28 2017

[113] A S Roccaro A R Blanco F Giuliano D Rusciano and VEnea ldquoEpigallocatechin-gallate enhances the activity of tetra-cycline in staphylococci by inhibiting its efflux from bacterialcellsrdquo Antimicrobial Agents and Chemotherapy vol 48 no 6pp 1968ndash1973 2004

[114] C Chu J Deng Y Man and Y Qu ldquoGreen tea extractsepigallocatechin-3-gallate for different treatmentsrdquo BioMedResearch International vol 2017 Article ID 5615647 9 pages2017

[115] A Furiga B Lajoie S El Hage G Baziard and C RoquesldquoImpairment of pseudomonas aeruginosa biofilm resistance toantibiotics by combining the drugs with a new quorum-sensinginhibitorrdquo Antimicrobial Agents and Chemotherapy vol 60 no3 pp 1676ndash1686 2016

[116] Y Inoue N Togashi and H Hamashima ldquoFarnesol-induceddisruption of the staphylococcus aureus cytoplasmic mem-branerdquo Biological and Pharmaceutical Bulletin vol 39 no 5 pp653ndash656 2016

[117] C Kim D Hesek M Lee and S Mobashery ldquoPotentiationof the activity of beta-lactam antibiotics by farnesol and itsderivativesrdquo Bioorganic amp Medicinal Chemistry Letters vol 28no 4 pp 642ndash645 2018

[118] G Brackman P Cos L Maes H J Nelis and T Coenye ldquoQuo-rum sensing inhibitors increase the susceptibility of bacterialbiofilms to antibiotics in vitro and in vivordquoAntimicrobial Agentsand Chemotherapy vol 55 no 6 pp 2655ndash2661 2011

[119] G Brackman K Breyne R De Rycke et al ldquoThe quorum sens-ing inhibitor hamamelitannin increases antibiotic susceptibilityof staphylococcus aureus biofilms by affecting peptidoglycanbiosynthesis and eDNA releaserdquo Scientific Reports vol 6 ArticleID 20321 2016

[120] J M Walz R L Avelar K J Longtine K L Carter L A Mer-mel and S O Heard ldquoAnti-infective external coating of centralvenous catheters A randomized noninferiority trial comparing

BioMed Research International 15

5-fluorouracil with chlorhexidinesilver sulfadiazine in pre-venting catheter colonizationrdquo Critical Care Medicine vol 38no 11 pp 2095ndash2102 2010

[121] C van Delden T Kohler F Brunner-Ferber B Francois JCarlet and J Pechere ldquoAzithromycin to prevent Pseudomonasaeruginosa ventilator-associated pneumonia by inhibition ofquorum sensing a randomized controlled trialrdquo Intensive CareMedicine vol 38 no 7 pp 1118ndash1125 2012

[122] A R Smyth P M Cifelli C A Ortori et al ldquoGarlic asan inhibitor of Pseudomonas aeruginosa quorum sensing incystic fibrosisndasha pilot randomized controlled trialrdquo PediatricPulmonology vol 45 no 4 pp 356ndash362 2010

Hindawiwwwhindawicom

International Journal of

Volume 2018

Zoology

Hindawiwwwhindawicom Volume 2018

Anatomy Research International

PeptidesInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Journal of Parasitology Research

GenomicsInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

The Scientific World Journal

Volume 2018

Hindawiwwwhindawicom Volume 2018

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Neuroscience Journal

Hindawiwwwhindawicom Volume 2018

BioMed Research International

Cell BiologyInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Biochemistry Research International

ArchaeaHindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Genetics Research International

Hindawiwwwhindawicom Volume 2018

Advances in

Virolog y Stem Cells International

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Enzyme Research

Hindawiwwwhindawicom Volume 2018

International Journal of

MicrobiologyHindawiwwwhindawicom

Nucleic AcidsJournal of

Volume 2018

Submit your manuscripts atwwwhindawicom

14 BioMed Research International

[93] X Zhang S Ou-yang JWang L Liao RWu and JWei ldquoCon-struction of antibacterial surface via layer-by-layer methodrdquoCurrent Pharmaceutical Design vol 24 no 8 pp 926ndash935 2018

[94] C Pustelny A Albers K Buldt-Karentzopoulos et al ldquoDiox-ygenase-mediated quenching of quinolone-dependent quorumsensing in pseudomonas aeruginosardquoChemistry amp Biology vol16 no 12 pp 1259ndash1267 2009

[95] J T Hodgkinson W R Galloway M Welch and DR Spring ldquoMicrowave-assisted preparation of the quorum-sensing molecule 2-heptyl-3-hydroxy-4(1H)-quinolone andstructurally related analogsrdquo Nature Protocols vol 7 no 6 pp1184ndash1192 2012

[96] F Witzgall T Depke M Hoffmann et al ldquoThe alkylquinolonerepertoire of Pseudomonas aeruginosa is linked to structuralflexibility of the fabh-like 2-heptyl-3-hydroxy-4(1H)-quinolone(PQS) biosynthesis enzyme PqsBCrdquo ChemBioChem vol 19 no14 pp 1531ndash1544 2018

[97] L Andresen E Sala V Koiv and A Mae ldquoA role for theRcs phosphorelay in regulating expression of plant cell walldegrading enzymes in Pectobacterium carotovorum subspcarotovorumrdquoMicrobiology vol 156 no 5 pp 1323ndash1334 2010

[98] L Andresen V Koiv T Alamae and A Mae ldquoThe Rcs phos-phorelay modulates the expression of plant cell wall degradingenzymes and virulence in Pectobacterium carotovorum sspcarotovorumrdquo FEMS Microbiology Letters vol 273 no 2 pp229ndash238 2007

[99] R K Gupta S Chhibber and K Harjai ldquoAcyl homoserinelactones from culture supernatants of pseudomonas aeruginosaaccelerate host immunomodulationrdquo PLoS ONE vol 6 no 6Article ID e20860 2011

[100] G F Kaufmann J Park J M Mee R J Ulevitch and KD Janda ldquoThe quorum quenching antibody RS2-1G9 protectsmacrophages from the cytotoxic effects of the Pseudomonasaeruginosa quorum sensing signalling molecule N-3-oxo-dodecanoyl-homoserine lactonerdquo Molecular Immunology vol45 no 9 pp 2710ndash2714 2008

[101] S Koul J Prakash A Mishra and V C Kalia ldquoPotential emer-gence of multi-quorum sensing inhibitor resistant (MQSIR)bacteriardquo Indian Journal of Microbiology vol 56 no 1 pp 1ndash182016

[102] T Praneenararat A G Palmer and H E Blackwell ldquoChemicalmethods to interrogate bacterial quorum sensing pathwaysrdquoOrganicampBiomolecular Chemistry vol 10 no 41 pp 8189ndash81992012

[103] J Park R Jagasia G F Kaufmann et al ldquoInfection controlby antibody disruption of bacterial quorum sensing signalingrdquoChemistry amp Biology vol 14 no 10 pp 1119ndash1127 2007

[104] C Grandclement M Tannieres S Morera Y Dessaux DFaure andM Camara ldquoQuorum quenching role in nature andapplied developmentsrdquo FEMSMicrobiology Reviews vol 40 no1 pp 86ndash116 2016

[105] MHan J GuG F Gao andW J Liu ldquoChina in action nationalstrategies to combat against emerging infectious diseasesrdquoScience China Life Sciences vol 60 no 12 pp 1383ndash1385 2017

[106] J Liu H Yu Y Huang et al ldquoComplete genome sequence ofa novel bacteriophage infecting Bradyrhizobium diazoefficiensUSDA110rdquo Science China Life Sciences vol 61 no 1 pp 118ndash1212018

[107] L D Christensen M van Gennip T H Jakobsen et alldquoSynergistic antibacterial efficacy of early combination treat-ment with tobramycin and quorum-sensing inhibitors against

Pseudomonas aeruginosa in an intraperitoneal foreign-bodyinfection mouse modelrdquo Journal of Antimicrobial Chemother-apy vol 67 no 5 pp 1198ndash1206 2012

[108] J Fong M Yuan T H Jakobsen et al ldquoDisulfide bond-containing ajoene analogues as novel quorum sensinginhibitors of Pseudomonas aeruginosardquo Journal of MedicinalChemistry vol 60 no 1 pp 215ndash227 2017

[109] R Garcıa-Contreras M Martınez-Vazquez N VelazquezGuadarrama et al ldquo Resistance to the quorum-quenchingcompounds brominated furanone C-30 and 5-fluorouracil inPseudomonas aeruginosa clinical isolates rdquo Pathogens and Dis-ease vol 68 no 1 pp 8ndash11 2013

[110] T H Jakobsen S K Bragason R K Phipps et al ldquoFood as asource for quorum sensing inhibitors iberin from horseradishrevealed as a quorum sensing inhibitor of pseudomonas aerug-inosardquo Applied and Environmental Microbiology vol 78 no 7pp 2410ndash2421 2012

[111] A Vadekeetil H Saini S Chhibber and K Harjai ldquo Exploitingthe antivirulence efficacy of an ajoene-ciprofloxacin combina-tion against Pseudomonas aeruginosa biofilm associatedmurineacute pyelonephritis rdquo Biofouling vol 32 no 4 pp 371ndash3822016

[112] S Bahari H Zeighami H Mirshahabi S Roudashti and FHaghi ldquoInhibition of pseudomonas aeruginosa quorum sensingby subinhibitory concentrations of curcumin with gentamicinand azithromycinrdquo Journal of Global Antimicrobial Resistancevol 10 pp 21ndash28 2017

[113] A S Roccaro A R Blanco F Giuliano D Rusciano and VEnea ldquoEpigallocatechin-gallate enhances the activity of tetra-cycline in staphylococci by inhibiting its efflux from bacterialcellsrdquo Antimicrobial Agents and Chemotherapy vol 48 no 6pp 1968ndash1973 2004

[114] C Chu J Deng Y Man and Y Qu ldquoGreen tea extractsepigallocatechin-3-gallate for different treatmentsrdquo BioMedResearch International vol 2017 Article ID 5615647 9 pages2017

[115] A Furiga B Lajoie S El Hage G Baziard and C RoquesldquoImpairment of pseudomonas aeruginosa biofilm resistance toantibiotics by combining the drugs with a new quorum-sensinginhibitorrdquo Antimicrobial Agents and Chemotherapy vol 60 no3 pp 1676ndash1686 2016

[116] Y Inoue N Togashi and H Hamashima ldquoFarnesol-induceddisruption of the staphylococcus aureus cytoplasmic mem-branerdquo Biological and Pharmaceutical Bulletin vol 39 no 5 pp653ndash656 2016

[117] C Kim D Hesek M Lee and S Mobashery ldquoPotentiationof the activity of beta-lactam antibiotics by farnesol and itsderivativesrdquo Bioorganic amp Medicinal Chemistry Letters vol 28no 4 pp 642ndash645 2018

[118] G Brackman P Cos L Maes H J Nelis and T Coenye ldquoQuo-rum sensing inhibitors increase the susceptibility of bacterialbiofilms to antibiotics in vitro and in vivordquoAntimicrobial Agentsand Chemotherapy vol 55 no 6 pp 2655ndash2661 2011

[119] G Brackman K Breyne R De Rycke et al ldquoThe quorum sens-ing inhibitor hamamelitannin increases antibiotic susceptibilityof staphylococcus aureus biofilms by affecting peptidoglycanbiosynthesis and eDNA releaserdquo Scientific Reports vol 6 ArticleID 20321 2016

[120] J M Walz R L Avelar K J Longtine K L Carter L A Mer-mel and S O Heard ldquoAnti-infective external coating of centralvenous catheters A randomized noninferiority trial comparing

BioMed Research International 15

5-fluorouracil with chlorhexidinesilver sulfadiazine in pre-venting catheter colonizationrdquo Critical Care Medicine vol 38no 11 pp 2095ndash2102 2010

[121] C van Delden T Kohler F Brunner-Ferber B Francois JCarlet and J Pechere ldquoAzithromycin to prevent Pseudomonasaeruginosa ventilator-associated pneumonia by inhibition ofquorum sensing a randomized controlled trialrdquo Intensive CareMedicine vol 38 no 7 pp 1118ndash1125 2012

[122] A R Smyth P M Cifelli C A Ortori et al ldquoGarlic asan inhibitor of Pseudomonas aeruginosa quorum sensing incystic fibrosisndasha pilot randomized controlled trialrdquo PediatricPulmonology vol 45 no 4 pp 356ndash362 2010

Hindawiwwwhindawicom

International Journal of

Volume 2018

Zoology

Hindawiwwwhindawicom Volume 2018

Anatomy Research International

PeptidesInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Journal of Parasitology Research

GenomicsInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

The Scientific World Journal

Volume 2018

Hindawiwwwhindawicom Volume 2018

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Neuroscience Journal

Hindawiwwwhindawicom Volume 2018

BioMed Research International

Cell BiologyInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Biochemistry Research International

ArchaeaHindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Genetics Research International

Hindawiwwwhindawicom Volume 2018

Advances in

Virolog y Stem Cells International

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Enzyme Research

Hindawiwwwhindawicom Volume 2018

International Journal of

MicrobiologyHindawiwwwhindawicom

Nucleic AcidsJournal of

Volume 2018

Submit your manuscripts atwwwhindawicom

BioMed Research International 15

5-fluorouracil with chlorhexidinesilver sulfadiazine in pre-venting catheter colonizationrdquo Critical Care Medicine vol 38no 11 pp 2095ndash2102 2010

[121] C van Delden T Kohler F Brunner-Ferber B Francois JCarlet and J Pechere ldquoAzithromycin to prevent Pseudomonasaeruginosa ventilator-associated pneumonia by inhibition ofquorum sensing a randomized controlled trialrdquo Intensive CareMedicine vol 38 no 7 pp 1118ndash1125 2012

[122] A R Smyth P M Cifelli C A Ortori et al ldquoGarlic asan inhibitor of Pseudomonas aeruginosa quorum sensing incystic fibrosisndasha pilot randomized controlled trialrdquo PediatricPulmonology vol 45 no 4 pp 356ndash362 2010

Hindawiwwwhindawicom

International Journal of

Volume 2018

Zoology

Hindawiwwwhindawicom Volume 2018

Anatomy Research International

PeptidesInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Journal of Parasitology Research

GenomicsInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

The Scientific World Journal

Volume 2018

Hindawiwwwhindawicom Volume 2018

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Neuroscience Journal

Hindawiwwwhindawicom Volume 2018

BioMed Research International

Cell BiologyInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Biochemistry Research International

ArchaeaHindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Genetics Research International

Hindawiwwwhindawicom Volume 2018

Advances in

Virolog y Stem Cells International

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Enzyme Research

Hindawiwwwhindawicom Volume 2018

International Journal of

MicrobiologyHindawiwwwhindawicom

Nucleic AcidsJournal of

Volume 2018

Submit your manuscripts atwwwhindawicom

Hindawiwwwhindawicom

International Journal of

Volume 2018

Zoology

Hindawiwwwhindawicom Volume 2018

Anatomy Research International

PeptidesInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Journal of Parasitology Research

GenomicsInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

The Scientific World Journal

Volume 2018

Hindawiwwwhindawicom Volume 2018

BioinformaticsAdvances in

Marine BiologyJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Neuroscience Journal

Hindawiwwwhindawicom Volume 2018

BioMed Research International

Cell BiologyInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Biochemistry Research International

ArchaeaHindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Genetics Research International

Hindawiwwwhindawicom Volume 2018

Advances in

Virolog y Stem Cells International

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Enzyme Research

Hindawiwwwhindawicom Volume 2018

International Journal of

MicrobiologyHindawiwwwhindawicom

Nucleic AcidsJournal of

Volume 2018

Submit your manuscripts atwwwhindawicom