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Thu Betteridge1, Sally R.Partridge2, Jon R.Iredell2,
and H.W.Stokes1
The I3 Institute, University of Technology, Sydney1.
Centre for Infectious Diseases & Microbiology, University of
Sydney, Westmead Hospital2
• An increased incidence of hospital infection and global spread of drug-
resistant bacteria
• Lateral Genetic Transfer (LGT):
- is an inherent process among bacteria to generate genetic
diversity
- becomes the driving force for generation and dissemination of
resistance genes
2
3
Genomic island
Transposons
Plasmids
ICEs
Integrons
IS elements
Mechanism of Genes Exchange:
• Conjugation
• Transformation
• Transduction
Mechanism of Genes Incorporation:
• Autonomous replication
• Transposition
• Site-specific recombination
• Homologous recombination
4
Integrase +
attC
Cassette 2 A two-component system
intl
attI
Pc
Pint
attC2 attC1
etc…
5
Chromosomal
integron?
IRt tniR tniQ tniB tniA IRi
IRi
qacEΔ1 sul1 orf5-(orf6)
5′-CS
attI1 3′-CS Δtni module
attI1 Cassette(s)
qacE (?)
Cassette(s)
IRt
Pre-clinical type
Clinical class 1 integrons
6
Genomic island
Transposons
Plasmids
ICEs
Integrons
IS elements
Mechanism of Genes Exchange:
• Conjugation
• Transformation
• Transduction
Mechanism of Genes Incorporation:
• Autonomous replication
• Transposition
• Site-specific recombination
• Homologous recombination
7
Chromosomal
integron?
IRt tniR tniQ tniB tniA IRi
IRi
qacEΔ1 sul1 orf5-(orf6)
5′-CS
attI1 3′-CS Δtni module
attI1 Cassette(s)
qacE (?)
Cassette(s)
IRt
Pre-clinical type
Clinical class 1 integrons
8
• Is there a presence of pre-clinical type integrons
(contains a full tni module) in the human commensal bacterial population?
• If so, do they have the same tni modules as seen in Tn402 ? What type
of gene cassette(s) are they carrying?
9
IRt IRi
5′-CS
attI1
3′-CS Δtni module Cassette(s)
3'-CS primers Tn402-tni module primers
Cassettes array primers
3'-CS tni module Cassettes
+ + +
+ - +
- - +
- + -
- - -
No. of
occurrences
9
9
3
4
9
Typical
Variant
10
IRt
100% Tn402-like (3)
IRt
Tn6005-like (3)
IRt
pOZ172-like
(none)
tniR tniQ tniB tniA
res
89%
84%
100% to Tn5053
11
dfrB3 gcuD qacE Tn402 in clinical strain (Klebsiella aerogenes)
IRi attI1
IRt
Full tni module Cassette(s)
Tn402
qacE 3 isolates (Klebsiella pneumonia)
(Escherichia coli) (Enterobacter sp.)
Our study
12
JKB7 in commensal strain (Enterobacter cloacae)
IRt
JKB007 qacG
IRi attI1
Full tni module Cassette(s)
tniR tniQ tniB tniA
2 isolates (Escherichia coli)
Tn6005
1 isolates (Enterobacter sp.)
Our study JKB007 qacG
13
blaIMP-4-qacG-aacA4-aphA15 pOZ172 in clinical strain (Citrobacter youngae)
aacA4-blaVIM-2 pPVV2-2 in clinical strain (Pseudomonas putida)
IRi attI1
IRt
Cassette(s)
pOZ172-like (with the hybrid Tn402/Tn5053 tni module)
tniR tniQ tniB tniA
14
dfrB3 gcuD qacE clinical strain (Enterobacter aerogenes)
IRi attI1
IRt
Full tni module Cassette(s)
qacE commensal strain (Klebsiella pneumonia)*
Tn402-like transposons
blaVIM-2 aacA4 clinical strain (Pseudomonas putida)
orf1 orf1 aadA6 environmental strain (Comomonas testosteroni)
orf3 qacF environmental strain (Pseudomonas alcaligenes)
orfB orf132 environmental strain (Pseudomonas sp.)
18
• Class 1 integrons with full tni module are more common than previously realised
• Site-specific recombination within the tni modules between members of the
Tn402/Tn5053 res hunter transposon family calls for more attention to these variant
integrons
• Class 1 integrons with full tni modules are dispersed to a wide range of bacterial species
and the varying gene cassette(s) content suggesting a dynamic gene flow from
environmental bacteria to human commensals and pathogens
• Detection and characterisation of gene cassette(s) from these variant Class 1 integrons
may help to predict the emergence of new resistant or virulent determinants before they
become prominent in bacterial populations
Thu Betteridge1, Sally R.Partridge2, Jon R.Iredell2,
and H.W.Stokes1
The I3 Institute, University of Technology, Sydney1. Centre for
Infectious Diseases & Microbiology, University of Sydney,
Westmead Hospital2