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Antimicrobial resistance ofStaphylococcuspseudintermedius

Kristina Kadlec and Stefan Schwarz

Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut (FLI), Ho ltystrae 10, 31535 Neustadt-Mariensee, Germany

Correspondence: Kristina Kadlec, Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut (FLI), Holtystrae 10, 31535 Neustadt-Mariensee,

Germany. E-mail: [email protected]

Staphylococcus pseudintermedius,Staphylococcus intermediusand Staphylococcus delphinitogether comprise

the S. intermediusgroup (SIG). Within the SIG, S. pseudintermedius represents the major pathogenic species

and is involved in a wide variety of infections, mainly in dogs, but to a lesser degree also in other animal species

and humans.

Antimicrobial agents are commonly applied to control S. pseudintermedius infections; however, during recent

yearsS. pseudintermedius isolates have been identified that are meticillin-resistant and have also proved to be

resistant to most of the antimicrobial agents approved for veterinary applications.

This review deals with the genetic basis of antimicrobial resistance properties in S. pseudintermediusand other

SIG members. A summary of the known resistance genes and their association with mobile genetic elements is

given, as well as an update of the known resistance-mediating mutations. These data show that, in contrast to

other staphylococcal species, S. pseudintermediusseems to prefer transposon-borne resistance genes, which

are then incorporated into the chromosomal DNA, over plasmid-located resistance genes.

Introduction

First described in 2005 as a novel species,1 Staphylococcus

pseudintermediusalong with another two coagulase-posi-

tive staphylococcal species, Staphylococcus intermedius

and Staphylococcus delphini, forms the S. intermediusgroup (SIG). Members of the SIG have been identified in a

variety of animal species, either as colonizers or as causa-

tive agents of diseases, very often skin infections.26

Despite the fact that a correct species identification within

the SIG requires molecular tools, the aforementioned stud-

ies have confirmed that S. pseudintermedius is most

frequently detected in dogs. Thus, Devrieseet al.7 recom-

mended that a canine isolate should be classified as

S. pseudintermediuswhen it is identified by standard tests

to belong to the SIG. In the present review, we also include

older publications and address the corresponding isolates

as S. pseudintermedius if they originate from dogs. Iso-

lates from other animal species will be referred to as SIGisolates in this review.

During recent years, the species S. pseudintermedius

has gained considerable attention because of the emer-

gence of meticillin-resistant S. pseudintermedius(MRSP)

isolates. The MRSP usually exhibit resistance to several

other non-b-lactam antimicrobial agents also. So far, most

of the publications on antimicrobial resistance in MRSP

have focused on isolates from dogs, and only few isolates

from other animals have been investigated. However,

resistant S. pseudintermediusisolates have been identi-

fied from several host species, including cats, horses, a

parrot, a donkey and humans.6,811 In contrast to dogs,

S. pseudintermedius seems to be very rare in some of

these species. In horses, for example, a single S. pseud-

intermediusisolate was identified between 1995 and 2006

from 3457horse post mortem examinations, among whichcoagulase-positive staphylococci were identified in 60

cases; the remaining isolates were Staphylococcus

aureus.8 The presence of indistinguishable isolates in pets

and their owners has been confirmed.12,13 Like other

staphylococci,S. pseudintermediusis a facultative patho-

gen, and resistant isolates have been identified as causa-

tive agents in clinical infections. In addition to canine

pyoderma, resistant S. pseudintermedius isolates have

been shown to cause complicated postoperative infec-

tions or skin infections in dogs and cats,14 urinary tract

infections in cats15 and various infections in human

patients.1618

In contrast to the wealth of data on phenotypic antimi-crobial resistance of S. pseudintermedius and SIG iso-

lates, comparatively little information is available on the

genetic basis of antimicrobial resistance. This report

reviews the current knowledge of the resistance genes

and the resistance-mediating mutations currently known

to occur inS. pseudintermediusand SIG isolates.

Phenotypic analysis of antimicrobialresistance inS. pseudintermediusand SIGisolates

Various studies have dealt with the phenotypic analysis of

antimicrobial resistance of S. pseudintermediusand SIGisolates.6,9,10,12,1925 For this, different methods have

Accepted 3 April 2012

Sources of Funding:This study was self-funded.Conflict of Interest:No conflicts of interest have been declared.

2012 The Authors. Veterinary Dermatology

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been used, including disk diffusion, broth microdilution

and, in selected cases and for specific antimicrobial

agents, the Etest. The use of the different methods

followed different performance standards, among which

the Clinical and Laboratory Standards Institute (CLSI) doc-

ument M31-A326 is most frequently used worldwide.

Moreover, different test panels of antimicrobial agents

and, for broth microdilution, different ranges of test con-

centrations for the antimicrobial agents have been used

in different studies. In addition, a wide range of inter-

pretive criteria have been used for the assessment of an

isolate as susceptible, intermediate or resistant to a spe-

cific antimicrobial agent. These observations underline

the problem of comparability of the results obtained in

different studies.27,28

The CLSI document M31-A3 contains only a few veteri-

nary-specific clinical breakpoints applicable to canine

S.[pseud]intermedius, e.g. for ampicillin and cefpodox-

ime.26 The interpretation of antimicrobial susceptibility

test results for other antimicrobial agents obtained from

S. pseudintermedius or SIG isolates usually relies on

breakpoints applicable to S. aureus, coagulase-negative

staphylococci or Staphylococcus spp.staphylococci in

general. In the absence of S. pseudintermedius-specific

interpretive criteria, it seems to be appropriate to use

breakpoints forS. aureus.

However, an exception is the identification of MRSP

isolates. Besides phenotypic oxacillin resistance, the

gene mecA has to be present to classify an isolate as

MRSP. For S. aureus and coagulase-negative staphylo-

cocci, the cefoxitin disk test is commonly used for predic-

tion of mecA-mediated resistance. A closer look at the

situation in MRSP has shown that the oxacillin break-

points recommended for S. aureus underestimate thepresence ofmecA-carryingS. pseudintermedius, and the

breakpoints given for coagulase-negative staphylococci,

namely minimal inhibitory concentration (MIC) values of

0.5 mgL and inhibitory zones of 17 mm, when test-

ing according to the CLSI document M31-A3, are much

more appropriate.22 Moreover, the cefoxitin predictive

test proved not to be useful for S. pseudintermedius.22

A revised recommendation is going to be included in the

forthcoming CLSI document M31-A4.

Genetic basis of antimicrobial resistance inS. pseudintermediusand SIG isolates

While many recent studies have focused on MRSP

isolates, comparatively little is known about the molecular

basis of antimicrobial resistance in meticillin-susceptible

S. pseudintermediusor SIG isolates. The following para-

graphs are intended to provide an update of the current

knowledge of the genes and mutations involved in the

resistance of meticillin-resistant and meticillin-susceptible

S. pseudintermediusor SIG isolates to various antimicro-

bial agents.

Resistance tob-lactam antibiotics

Based on CLSI recommendations, meticillin (oxacillin)-

resistant staphylococci are considered as resistant to allb-lactam antibiotics. As such, resistance to the penicillin-

ase-stable penicillins meticillin and oxacillin has gained

particular attention. In laboratory testing, meticillin has

been replaced by the more stable oxacillin. Studies

conducted during the years 19861995 did not identify

oxacillin-resistantS. pseudintermediusor SIG isolates.29

Moreover, no oxacillin-resistant isolate was detected

among 50 S. pseudintermedius isolates from cases of

canine pyoderma collected in 2002.25 However, an

increasing number of MRSP isolates has been identified

during the last decade.30,31 A retrospective investigation

showed an increase from about 5 to 30% among iso-

lates from the USA during the years 2001 to 2007,

respectively.22 High rates of meticillin-resistant S. pseud-

intermediuswere seen, with 17% in isolates from 2003

200432 and 15.6% in isolates from 2005.33 The first case

of a meticillin-resistant S. pseudintermedius in Europe

was published in 2007.24 Meticillin-resistant S. pseudin-

termedius is regarded a nosocomial bacterium in veteri-

nary clinics, in a similar way to healthcare-associated

meticillin-resistant S. aureus (MRSA) in human hospital

settings.19,34

Meticillin resistance is based on the expression of the

mecA gene, which codes for the alternative penicillin-

binding protein PBP2a. The mecA gene is located on a

mobile genetic element, the staphylococcal cassette

chromosomemec(SCCmec) element. The types of these

SCCmecelements present in MRSP seem to differ from

those identified in MRSA. Two of these SCCmec ele-

ments from MRSP were sequenced completely and

proved to be novel types of SCCmecelements. The one

found in S. pseudintermedius KM1381 was composed

exclusively of parts previously identified in SCCmecele-

ments of types II and III; it was designated as type II

III.35 The SCCmecelement found inS. pseudintermedius

KM241 also showed partial homology to SCCmectype IIIbut, based on the structural differences and the novel ccr

gene complexccrA5ccrB5, was considered to represent

a novel type, designated SCCmecVII35 and subsequently

renamed SCCmecKM-241.19 In contrast to the SCCmec

elements of types II or III,36 the SCCmec elements of

types IIIII and VII did not carry integrated Tn554-like

transposons or small resistance plasmids, such as the

aadD-carrying kanamycinneomycin resistance plasmid

pUB110 or thetet(K)-carrying tetracycline resistance plas-

mid pT181. The analysis of 103 canine MRSP isolates

from Europe and North America identified the hybrid

SCCmecelement IIIII in 75 (72.8%) isolates, while the

remaining isolates either had SCCmectypes III (n = 2), IV(n = 6), V (n = 14) or VII (n = 4) or were not typeable

(n = 2).19 The analysis of feline MRSP from Europe and

North America identified the SCCmecelement IIIII in the

11 isolates from Europe, whereas the single isolate from

Canada had an SCCmecelement of type V.9 Two recent

studies on MRSP among dogs and cats admitted to a vet-

erinary hospital during a 17 month period also identified

the SCCmecelement of type IIIII in all 69 canine and

three feline MRSP isolates.10,20

Resistance to penicillinase-labile penicillins, such as

penicillin G, ampicillin or amoxicillin, seems to be fre-

quent in S. pseudintermedius. An investigation of 116

canine isolates from Germany and the USA identified 72(62.1%) as ampicillin resistant.37 A similar percentage

was seen among isolates from France, where 31 (62.0%)


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of 50 isolates were found to be b-lactamase producers.25

Microarray studies of MRSP isolates revealed that the

geneblaZ, which codes for a narrow-spectrum b-lactam-

ase, is present in most of the MRSP isolates, e.g. in 102

(99.0%) of 103 canine MRSP and all 12 feline MRSP iso-

lates from Europe and North America.9,19 The gene blaZ

was also detected by PCR in MRSP (n = 12) and meticillin-

susceptible S. pseudintermedius (MSSP; n = 3) from

dogsand inMRSP fromcats (n = 2).23

Resistance to tetracyclines

So far, four different tetracycline resistance genes have

been identified in S. pseudintermediusand SIG isolates.

The genes tet(K) and tet(L) code for efflux pumps

of the major facilitator superfamily, whereas the

genes tet(M) and tet(O) code for ribosome protective

proteins.38

Analysis of 301 S. pseudintermediusand SIG isolates

from dogs, cats, horses, mink and pigeons identified tet-

racycline resistance in 105 (34.9%) isolates. Among

them, the tet(M) gene was present in 89 (84.8%), the

tet(K) gene in five (4.8%), the tet(O) gene in one (0.9%),

the genestet(K) and tet(M) in eight (7.6%) and the genes

tet(L) and tet(M) in two (1.9%) isolates.39 In a study by

Kimet al.,40 29 of 144 tetracycline-resistant isolates were

tested for the presence of tetgenes, with the following

results: tet(M), n = 18; tet(M) and tet(K), n = 4; tet(M)

and tet(L), n = 6; and tet(L), n = 1. The gene tet(K),

which is commonly found on small plasmids in other

staphylococci from humans and animals,41 was identified

in a single canine S. pseudintermedius isolate to be

located on a 4.5 kb plasmid. This plasmid, designated

pSTS2, was virtually indistinguishable in its restriction

map from the S. aureus prototype plasmid pT181.

37

Further analysis of tetracycline-resistant canine S. pseud-

intermedius(n = 6) and equine SIG isolates (n = 3) identi-

fied the tet(M) gene on different-sized chromosomal

HindIII fragments in all nine isolates.39 The tet(M) gene

has been identified as part of conjugative transposons,

such as Tn916 and Tn1545.42 More recent studies on

canine and feline MRSP revealed that 72 (69.9%) of 103

canine and all 12 feline isolates were tetracycline resis-

tant. In these isolates, the genes tet(K) (50.5%), tet(M)

(17.5%) or, occasionally, tet(K) and tet(M) (1.9%) were

detected.9,19

Resistance to macrolides and lincosamidesSo far, five different genes that confer resistance to

macrolides andor lincosamides have been identified in

S. pseudintermediusand SIG isolates. Among them are

the gene lnu(A), which codes for a lincosamide nucleot-

idyl transferase, the gene msr(A), which codes for an

ABC transporter that can export macrolides and strep-

togramin B antibiotics, and the genes erm(A),erm(B) and

erm(C), all of which code for rRNA methylases that confer

combined resistance to macrolides, lincosamides and

streptogramin B antibiotics.

Previous studies identified the Tn917-associated

erm(B) gene as the predominant erm gene in canine and

felineS. pseudintermedius.

43,44

This gene was detectedas the sole macrolidelincosamide resistance gene in 10

and 21 caninefeline S. pseudintermedius isolates from

respiratory tract infections or skinearmouth infections,

respectively, collected in the BfT-GermVet study.44 More-

over, it was also the sole macrolidelincosamide resis-

tance gene in most canine and feline MRSP isolates from

Europe and North America.9,19 In six canine MRSP iso-

lates from the USA and Canada, the gene erm(B) was

present together with the gene lnu(A).19 In two canine

felineS. pseudintermedius isolates from skinearmouth

infections of the BfT-GermVet study, the gene erm(B)

was found together with the genemsr(A).44 Another two

caninefeline S. pseudintermedius isolates from respira-

tory tract infections harboured the gene erm(A),44 which

is usually linked to the spectinomycin resistance gene

spc in transposon Tn554.45 A constitutively expressed

erm(A) gene was also detected on a 70 kb plasmid in a

SIG isolate from a carrier pigeon.46 Theerm(C) gene was

detected on 2.5 kb plasmids in two canine S. pseudin-

termediusisolates.37 These plasmids were indistinguish-

able in their restriction maps and closely resembled the

erm(C)-carrying plasmid pNE131.47

Resistance to chloramphenicol

Chloramphenicol resistance in S. pseudintermedius and

SIG isolates is usually based on the expression of chlor-

amphenicol acetyltransferase (cat) genes. Among the

three catgenes known to occur in staphylococci,41 the

catgene originally identified on the 4.5 kb plasmid pC221

is very common. Small catpC221-carrying plasmids, rang-

ing in size between 3.1 and 4.1 kb, were identified in

canine S. pseudintermedius.37,48,49 These plasmids clo-

sely resembled pC221 in the parts comprising the plas-

mid replication gene and the catgene, but differed in the

remaining parts of the plasmids. Kim et al.40 identified

chloramphenicol resistance in 29 (18.1%) of 160 canineS. pseudintermediusisolates. In 17 of these 29 isolates,

a catpC221 was identified, which was often linked to a

pS94-like streptomycin resistance gene. This combination

of a catpC221 gene with a str gene had been observed

before in other staphylococcal species.50,51 The catpC221gene was also detected in 59 (57.3%) of the 103 canine

isolates and in 10 (83.3%) of the 12 feline MRSP isolates

from Europe and North America.9,19

Resistance to aminoglycosides

Different genes, all coding for aminoglycoside-inactivating

enzymes, have been identified in S. pseudintermedius

and SIG isolates. The gene aacA-aphD, also namedaac(6)-Ie-aph(2)-Ia, which confers resistance to gentami-

cin, tobramycin and kanamycin, has been identified in

canine MRSP isolates.19,52 Kanamycin resistance was

also conferred by the gene aphA-3, also named aph(3)-

III.19,43 In the study by Boerlin et al.,43 a gene cluster

carrying the gene aphA-3, the gene sat4 coding for a

streptothricin acetyltransferase and the gene aadE, also

named ant(6)-Ia, coding for a streptomycin adenyltrans-

ferase, was identified. This gene cluster showed homol-

ogy to the respective part of transposon Tn5405.43 In

close proximity to the right-hand terminus of this Tn5405-

homologous segment, the MLSBresistance gene erm(B)

was identified. This structure was seen in the chromo-somal DNA of 20 erythromycin- and aminoglycoside-

resistantS. pseudintermediusisolates.



Kadlec and Schwarz

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The analysis of MRSP for aminoglycoside resistance

genes identified theaacA-aphDgene in 91 (88.3%) of the

103 canine and in 11 (91.7%) of the 12 feline isolates

from Europe and North America. The resistance genes

aphA-3,sat4and aadEwere simultaneously present in 93

(90.3%) of the 103 canine and in 11 (91.7%) of the 12

feline MRSP isolates. The erm(B) gene was also present

in all but one canine isolate from Germany. These obser-

vations suggested that despite the wide geographical dis-

tribution, the vast majority of the MRSP isolates of dogs

and cats carried the erm(B) gene linked to a Tn5405-like

element.

Resistance to trimethoprim

Susceptibility testing to the combination sulfonamidetri-

methoprim is very common. In contrast, trimethoprim

resistance is rarely tested, because this antimicrobial

agent is not commonly available for therapeutic interven-

tions. Observations made in the BfT-GermVet study

showed that sulfamethoxazoletrimethoprim MIC values

of 476 mgL are seen only when staphylococcci are

resistant to both folate pathway inhibitors. Isolates resis-

tant to sulfonamides and susceptible to trimethoprim or

vice versa usually show distinctly lower sulfonamidetri-

methoprim MIC values.53,54 So far, the molecular basis

for sulfonamide resistance has not been identified in

S. pseudintermedius. For trimethoprim resistance, the

gene dfrGhas been detected in all 93 (90.3%) trimetho-

prim-resistant canine and in all 11 trimethoprim-resistant

feline MRSP isolates.9,19 The gene dfrG codes for a

trimethoprim-resistant dihydrofolate reductase. It was

described first in 2005 in a nosocomial S. aureus

isolate.55

Resistance to fluoroquinolones

In a study from France, 393 S. intermedius isolates were

collected in the years 1995, 1997 and 1999, and MICs to

enrofloxacin were determined.56 The MIC values of the

majority of isolates ranged from 0.063 to 1 mgL, with

only two isolates showing higher MIC values of 2 or

64 mgL. Both isolates were detected in 1999 and did

not show resistance to b-lactams.56 Among the canine

and feline MRSP isolates from Europe and North Amer-

ica, 90 (87.4) of the canine and 11 (91.7%) of the feline

isolates were classified as fluoroquinolone-resistant by

ciprofloxacin MIC values of 4 mgL.9,19 Descloux et

al.

35

identified numerous base pair exchanges in thegenes gyrA, gyrB, grlA and grlBof S. pseudintermedius

isolates with enrofloxacin MICs of 4 mgL. Some of

these base pair exchanges resulted in amino acid substi-

tutions at positions previously identified to play a role in

(fluoro)quinolone resistance; Ser84Leu and Glu88Gly in

gyrA and Ser80Ile and Asp84Asn in grlA.35 The same

exchanges, Ser84Leu and Glu88Gly in gyrA as well as

Ser80Ile and Asp84Asn in grlA, were seen in MRSP iso-

lates from Japan tested for their resistance to three fluro-

roquinolones (ofloxacin, enrofloxacin and levofloxacin). In

addition, Ser84Phe in gyrA and Asp84Glu in grlA were

detected in isolates classified as resistant or intermediate

to all three agents. In one isolate resistant to only ofloxa-cin, the exchange Ser81Pro was present ingrlA.57 Among

136 canine S. pseudintermedius isolates from Italy, two

were fluoroquinolone resistant and one of them showed

single amino acid substitutions in gyrA (Ser84Leu)

and grlA (Ser80Arg).58 The same two exchanges were

detected in three resistant S. pseudintermedius isolates

from Korea, while isolates considered as intermediate

showed solely the exchange in grlA.59 In eight ciprofloxa-

cin-resistant MRSP isolates from Spain (MIC of

32 mgL), these two substitutions were also identified.60

In addition, the seven isolates belonging to the MLST

type ST71 showed (in contrast to the remaining ST92

isolate) an additional exchange ingyrAGlu714Lys.60

Resistance to rifampicin

Comparatively little is known about rifampicin resistance

in canineS. pseudintermedius. Isolates resistant to rifam-

picin occur very rarely. Among 103 MRSP isolates from

dogs, only two isolates showed high rifampicin MIC

values of 64 mgL.19 A single in-depth study on the

genetics of rifampicin resistance in MRSP isolates is

currently available.61 The two MRSP isolates of the multi-

centre study19 showed amino acid substitutions at

positions 513 (Gln513Arg) or 522 (Ala522Asp) in the

rifampicin resistance-determining region of RpoB.61

During the screening of nine individual dogs, all rifampi-

cin-resistant MRSP isolates showed mutations at one or

two of the amino acid positions 508 (Ser508Asn), 509

(Ser509Pro), 513 (Glu513Leu), 516 (Asp516Asn), 522

(Ala522Asp), 526 (His526Arg, His526Pro, His526Tyr) and

531 (Ser531Leu). In most MRSP isolates, only a single

amino acid exchange was observed.61

Resistance to fusidic acid and mupirocin

Resistance to both fusidic acid and mupirocin seems to

be very rare. Loeffler et al.

62

investigated 71 MSSP and12 MRSP isolates for their MICs to fusidic acid and mup-

irocin. The MSSP and MRSP isolates varied in their MICs

of fusidic acid between 0.068 and 0.062 mgL, respec-

tively. Likewise, low mupirocin MICs of 0.064 and 0.06

0.5 mgL were recorded for the MSSP and MRSP

isolates, respectively.62 None of the 103 canine MRSP

isolates had an elevated MIC value of fusidic acid.19 A sin-

gle study is available in which fusidic acid resistance

based on the gene fusCwas detected in two S. pseudin-

termediusisolates.63

Conclusion

As outlined in the previous sections, a number of antimi-

crobial resistance genes have been detected in S. pseud-

intermedius (Table 1). Most of these resistance genes

have also been identified in other staphylococcal species

or bacteria of other Gram-positive genera and species.

This observation underlines the ability of S. pseudinter-

medius to acquire genetic material from other bacteria.

However, in contrast to other staphylococci,29,41,64,65

plasmids do not seem to play an important role as carriers

of antimicrobial resistance genes. Apart from a few

exceptions,37 resistance plasmids have rarely been

detected in S. pseudintermedius and SIG isolates. In

contrast, S. pseudintermediusseems to prefer transpo-son-borne antimicrobial resistance genes. Most of

the determined antimicrobial resistance genes in




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S. pseudintermediusand SIG isolates are associated with

transposons, as follows: blaZ, Tn552; tet(M), Tn916and

Tn1545; erm(A), Tn554; erm(B), Tn917and Tn551; aacA-

aphD, Tn4001; and aphA-3, sat4and aadE, Tn5405.41,64

InS. pseudintermedius, these transposons integrate into

the chromosomal DNA and are replicated as part of the

S. pseudintermedius genome. Comparative studies of

horizontal gene transfer using S. aureus, S. pseudinter-

medius and Staphylococcus hyicusstrains as recipientsshowed that plasmid transfer to S. pseudintermedius

occurred at much lower frequencies than to S. aureusor

S. hyicus, whereas a presumed transposon transfer

directly to the chromosome occurred at almost equal fre-

quencies in all three species.66 These observations sug-

gest that S. pseudintermedius might have developed

ways and means to protect itself from extrachromosomal

DNA. The analysis of the recently finished whole genome

sequences of S. pseudintermedius isolates67,68 will pro-

vide insight into the presence of restrictionmodification

systems or similar systems that might execute such a

protective function.

As shown in the studies of Perreten et al.

19

and Kadlecet al.,9 the accumulation of resistance genes and resis-

tance-mediating mutations, currently found especially in

contemporary MRSP isolates from dogs and cats, ren-

ders these isolates resistant to virtually all antimicrobial

agents available for therapeutic interventions in veterinary

medicine. As such, the control of MRSP infections has

become a real challenge for the veterinary practitioner.

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Table 1. Antimicrobial resistance genes and resistance-mediating

mutations inS. pseudintermediusandS. intermediusgroup isolates

Class of

antimicrobial

agents

Resistance

gene Resistance mechanism

b-Lactam

antibiotics

mecA Alternative target with low affinity

tob-lactam antibiotics

blaZ Inactivation of penicillins by

hydrolysis

Tetracyclines tet(M) Target protection by ribosome

protective protein

tet(O) Target protection by ribosome

protective protein

tet(K) Efflux system (major facilitator

superfamily)

tet(L) Efflux system (major facilitator

superfamily)

Macrolides and

lincosamides

erm(A) Methylation of 23S rRNA

erm(B) Methylation of 23S rRNA

erm(C) Methylation of 23S rRNA

msr(A) Efflux system (ABC transporter)

lnu(A) Inactivation of lincosamides by

nucleotidylation

Chloramphenicol catpC221 Inactivation by acetylation

Aminoglycosides aacA-aphD Inactivation of gentamicin,

tobramycin and kanamycin by

acetylationphosphorylation

aphA-3 Inactivation of kanamycin by

phosphorylation

sat4 Inactivation of streptothricin by

acetylation

aadE Inactivation of streptomycin by

adenylation

Trimethoprim dfrG Alternative insensitive target

(dihydrofolate reductase)

Fluoroquinolones n.a. Mutations in the genesgyrA,gyrB,

grlA andgrlB

Rifampicin n.a. Mutations in the generpoB

Fusidic acid fusC Target protection by binding to

elongation factor G

n.a., not applicable.



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Resume

Staphylococcus pseudintermedius, Staphylococcus intermedius et Staphylococcus delphini forment le

groupeS. intermedius(SIG). Au sein du SIG, S. pseudintermediusrepresente la principale espece patho-

gene impliquee dans une grande varietedinfections, principalement chez les chiens et dans une moindre

mesure dans dautres especes animales et chez lhomme.

Les agents antimicrobiens sont frequemment utilises pour controler des infections aS. pseudintermedius.

Cependant, au cours de ces dernieres annees, les souches de S. pseudintermediusidentifiees comme

resistantes a la meticilline se sont egalement averees etre resistantes a la plupart des agents antimicrob-

iens valides ausage veterinaire.

Cette revue porte sur les bases genetiques des proprietes de resistance aux antimicrobiens de S. pseudin-

termediuset des autres membres du SIG. Un resumedes genes de resistance actuellement connus, leurassociation avec les elements genetiques mobiles ainsi quune mise a jour des resistances mediees par

mutation connues jusqua ce jour sont rappeles. Ces donnees montrent que contrairement aux autres

especes de staphylocoques, S. pseudintermediussemble preferer les genes de resistance portes par

des transposons inseres au sein du chromosome, au-dessus de genes de resistances portes par des

plasmides.

Resumen

Staphylococcus pseudintermediusforma junto conStaphylococcus intermediusy Staphylococcus delphini

el grupoS. intermedius(SIG). Dentro de los SIG,S. pseudintermediusrepresenta la especie patogena mas

importante y estaimplicada en una amplia variedad de infecciones, principalmente en perros, pero tambien

en otras especies animales y en seres humanos.

El uso de agentes antimicrobianos es comun para el control de infecciones por S. pseudintermedius. Sin

embargo, durante los ultimos anos, se han identificado aislados de S. pseudintermedius resistentes a

meticilina y a la mayor parte de a los agentes antimicrobianos aprobados para uso veterinario.En esta revision se realiza un analisis de los fundamentos geneticos de la resistencia a antimicrobianos en

S. pseudintermediusas como en otros miembros del grupo SIG. Se resumen todos los genes conocidos

relacionados con la resistencia, as como su asociacion con elementos geneticos moviles. Tambien se

incluye una actualizacion de todas las mutaciones, conocidas hasta el momento, relacionas con mecanis-

mos de resistencia. Estos datos demuestran, en contraste con lo que ocurre en otras especie de estafilo-

cocos, que S. pseudintermediusparece preferir genes de resistencia en transposones, que despues se

incorporan al ADN cromosomico, frente a genes localizados en plasmidos.

Zusammenfassung

Staphylococcus pseudintermediusbildet zusammen mit Staphylococcus intermediusund Staphylococcus

delphinidie S. intermediusGruppe (SIG). Innerhalb der SIG reprasentiertS. pseudintermediusdie wichtig-

ste pathogene Spezies, die vor allem beim Hund an vielen verschiedenen Infektionen beteiligt ist. Das ist

auch in einem geringeren Ausma bei anderen Tierspezies und beim Menschen der Fall.Antimikrobielle Wirkstoffe werden haufig angewendet, um S. pseudintermedius Infektionen zu kon-



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trollieren. Insbesondere in den letzten Jahren wurden S. pseudintermedius Isolate identifiziert, die

Methicillin-resistent waren und sich auch als resistent gegenuber den meisten antimikrobiellen Wirkst-

offen, die veterinarmedizinisch zugelassen sind, erwiesen haben.

Dieses Review befasst sich mit der genetischen Basis der antimikrobiellen Resistenz von S. pseudinter-

medius und anderen Spezies aus der SIG. Eine Zusammenfassung der momentan bekannten Resistenz-

gene und ihre Verbindung mit mobilen genetischen Elementen, sowie ein Update der bisher bekannten

Resistenz-vermittelnden Mutationen werden prasentiert. Diese Daten zeigen, dass S. pseudintermedius

im Gegensatz zu anderen Staphylokokken-Spezies scheinbar Resistenzgene, die in Transposons lokalisiert

sind, und in die chromosomale DNA integriert werden, gegenuber Plasmid-lokalisierten bevorzugt.



2012 ESVD and ACVD, Veterinary Dermatology,23, 276e55. e55

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