Resistance gene mobility mechanisms Sally Partridge sally.partridge@health.nsw.gov.au CPATH 2015 Kuala Lumpur 13 th June 2015
Mobile resistance genes R R gene plasmid chromosome
Mobile resistance genes R R R gene plasmid chromosome
Mobile resistance genes R R R gene plasmid chromosome S R
Mobile resistance genes R R R gene plasmid chromosome R S R
two kinds of mobile genetic element R insertion sequence transposon integron/gene cassette conjugative plasmid mobilisable plasmid integrative conjugative element (ICE) S R
insertion sequence () IR L ISEcp1 ISCR (5 bp) IR L tnp IR R () tnp IR R () teris rcr IR alt tnp composite transposon tnp () IR tnp oriis (5 bp) Tn3-subgroup (5 bp) transposon tnpa tnpr res terminal inverted repeat (IR) antibiotic resistance gene IR (5 bp) Tn21-subgroup transposon (5 bp) IR tnp tnpa tnpr res mer or IR (5 bp) Tn5053-family transposon integron gene cassettes IRi (5 bp) 1In or mer tnir inti res tniq tnib atti cassette array attc tnia attc IRt (5 bp) Sally R. Partridge FEMS Microbiol Rev 2011;35:820-855 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved
Insertion sequences IR L transposase gene (tnpa) IR R
Insertion sequences IR IR transposase gene (tnpa) transposase
Insertion sequences IR IR transposase gene (tnpa) transposase + IR IR
direct repeats
direct repeats
direct repeats
direct repeats T T T A G T A A T T T A G T A A
Composite transposons IS
Composite transposons IS IS
Composite transposons IS IS + IS IS
ISEcp1 ISEcp1
ISEcp1 ISEcp1 + 5 or 6 bp 5 or 6 bp ISEcp1
ISEcp1 ISEcp1 + ISEcp1
ISEcp1 ISEcp1 + ISEcp1
ISEcp1 C. freundii ampr bla CMY-2 blc suge ecnrba TGGGT GATTA GATAA ISEcp1 ISEcp1 ISEcp1 bla CMY-2 bla CMY-36 bla CMY-2 TGGGT GATTA GATAA pcvm29188_101 (IncI) (2.254 kb) ph205 (ColE1-like) (2.369 kb) psc138 (IncI) (2.431 kb) ATTTC ISEcp1 bla CMY-2 ATTTC par060302 (IncA/C) (2.823 kb) ATTTG ISEcp1 bla CMY-2 E. coli ATTTG TN44889 (1.422 kb C. freundii plus 0.503 kb E. coli) Sally R. Partridge FEMS Microbiol Rev 2011;35:820-855 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved
IS91-like and ISCR elements ter rcr ori
IS91-like and ISCR elements IS91 IS801 IS1294 ter IS ori
IS91-like and ISCR elements =GTTC ter ori IS ter IS ori
IS91-like and ISCR elements ter IS ori ter IS ori +
IS91-like and ISCR elements ter IS ori ter IS ori + ter IS ori
Unit transposons IS IR L IR R tnpa
Unit transposons IS IR L IR R tnpa unit Tn (Tn3, Tn21 subfamilies) IR res site IR tnpa tnpr (resolvase)
The difference between IS and Tn? IS IR L IR R tnpa unit Tn (Tn3, Tn21 subfamilies) IR res site IR tnpa tnpr (resolvase) IR IR IR IR IR IR tnpa tnpr passenger genes tnpa Tn5403 ISKpn25
Unit transposons Tn2 Tn4401a IR tnp IR KPC tnpa tnpr IR TEM bla TEM-1b IRΔ ISKpn6 ISKpn7 bla KPC tnpa tnpr IR tnp IR tnp IR mer Tn5036 tnpa tnpr merde A C P T R Tn1721 IR tnp tnpaδ pecm tetar(a) IR tnp tnpa tnpr mcp IR mcp Tn1722 Tn402 -like IR res IR tnir tniq tnib tnia adapted from Partridge (2011) FEMS Microbiol Rev 35:820-55
Transposition of Tn tnpa res + tnpr
Transposition of Tn tnpa res tnpr + TnpA tnpa res tnpr tnpa res tnpr
Transposition of Tn tnpa res tnpr + TnpA tnpa tnpa res res tnpr TnpR tnpr
Transposition of Tn tnpa res tnpr + TnpA tnpa res tnpr TnpR tnpa res tnpr tnpa res tnpr + tnpa res tnpr
Minature inverted-repeat transposable elements IR IR res Tn tnpa tnpr MITE IR IR teta(a)
Gene cassette R gene recombination site (attc originally 59-base element )
Integron Pc atti inti RS
Integron inti Pc atti RS +
Integron inti Pc atti RS +
Integron inti Pc atti RS + +
Integron inti Pc atti RS + + cassette array
Class 1 integrons - Tn derivatives Tn402-like transposon IR tnir tniq tnib tnia atti1 + inti1 CA IR IRi 5'-CS CA qace tni 402 IRt IRi IRi CA 3'-CS CA qaceδ1 sul1 3'-CS orf5 6 IS IS tnibδ2 tnibδ1 IRt IRt Sally R. Partridge FEMS Microbiol Rev 2011;35:820-855 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved
associations between elements class 1 integron IRi CA 3'-CS tnibδ1 IRt + ISCR1 IRi CA 3'-CS1 ISCR1 3'-CS2 IRt Tn21 IR tnp tnpa TCCAT TCCAT tnpr urf2 merd E A C P T R IR mer
bla NDM contexts Partridge & Iredell AAC 2012;56:6065-7
Resistance plasmids maintenance stability replication incompatibility (Inc) group typing by PCR up to ~200 kb multi-resistance region (modular) mobilisation/ conjugation relaxase gene (MOB) typing
Homologous recombination + adapted from Partridge (2011) FEMS Microbiol Rev 35:820-55
IS26 IS26 IS26 based on Harmer, Moran, Hall (2014) mbio 5:e01801-14
IS26 IS26 IS26 IS26 based on Harmer, Moran, Hall (2014) mbio 5:e01801-14
IS26 IS26 IS26 IS26 + IS26 based on Harmer, Moran, Hall (2014) mbio 5:e01801-14
IS26 IS26 IS26 IS26 + IS26 IS26-35 IS26 based on Harmer, Moran, Hall (2014) mbio 5:e01801-14
IS26 IS26 IS26 transposase IS26 + IS26 IS26 IS26 based on Harmer, Moran, Hall (2014) mbio 5:e01801-14
Summary genes captured from various species mobile resistance genes each resistance gene usually associated with one particular mobile element (at least initially), which often provides a promoter mobile elements and associated resistance genes often cluster together in large, complex multi-resistance regions on plasmids evolution of multi-resistance regions and movement of resistance genes by actions of mobile elements + homologous recombination need to understand what is spreading single resistance gene, set of resistance genes, whole plasmid, strain?