Insertion Sequence IS<italic toggle="yes">26</italic> Reorganizes Plasmids in Clinically Isolated Multidrug-Resistant Bacteria by Replicative Transposition

ABSTRACT Carbapenemase-producing Enterobacteriaceae (CPE), which are resistant to most or all known antibiotics, constitute a global threat to public health. Transposable elements are often associated with antibiotic resistance determinants, suggesting a role in the emergence of resistance. One inse...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Susu He, Alison Burgess Hickman, Alessandro M. Varani, Patricia Siguier, Michael Chandler, John P. Dekker, Fred Dyda
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/4ada9d4fb9c148a89c22b1e6e88a328c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4ada9d4fb9c148a89c22b1e6e88a328c
record_format	dspace
spelling	oai:doaj.org-article:4ada9d4fb9c148a89c22b1e6e88a328c2021-11-15T15:49:02ZInsertion Sequence IS<italic toggle="yes">26</italic> Reorganizes Plasmids in Clinically Isolated Multidrug-Resistant Bacteria by Replicative Transposition10.1128/mBio.00762-152150-7511https://doaj.org/article/4ada9d4fb9c148a89c22b1e6e88a328c2015-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00762-15https://doaj.org/toc/2150-7511ABSTRACT Carbapenemase-producing Enterobacteriaceae (CPE), which are resistant to most or all known antibiotics, constitute a global threat to public health. Transposable elements are often associated with antibiotic resistance determinants, suggesting a role in the emergence of resistance. One insertion sequence, IS26, is frequently associated with resistance determinants, but its role remains unclear. We have analyzed the genomic contexts of 70 IS26 copies in several clinical and surveillance CPE isolates from the National Institutes of Health Clinical Center. We used target site duplications and their patterns as guides and found that a large fraction of plasmid reorganizations result from IS26 replicative transpositions, including replicon fusions, DNA inversions, and deletions. Replicative transposition could also be inferred for transposon Tn4401, which harbors the carbapenemase blaKPC gene. Thus, replicative transposition is important in the ongoing reorganization of plasmids carrying multidrug-resistant determinants, an observation that carries substantial clinical and epidemiological implications for understanding how such extreme drug resistance phenotypes evolve. IMPORTANCE Although IS26 is frequently reported to reside in resistance plasmids of clinical isolates, the characteristic hallmark of transposition, target site duplication (TSD), is generally not observed, raising questions about the mode of transposition for IS26. The previous observation of cointegrate formation during transposition implies that IS26 transposes via a replicative mechanism. The other possible outcome of replicative transposition is DNA inversion or deletion, when transposition occurs intramolecularly, and this would also generate a specific TSD pattern that might also serve as supporting evidence for the transposition mechanism. The numerous examples we present here demonstrate that replicative transposition, used by many mobile elements (including IS26 and Tn4401), is prevalent in the plasmids of clinical isolates and results in significant plasmid reorganization. This study also provides a method to trace the evolution of resistance plasmids based on TSD patterns.Susu HeAlison Burgess HickmanAlessandro M. VaraniPatricia SiguierMichael ChandlerJohn P. DekkerFred DydaAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 3 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Susu He Alison Burgess Hickman Alessandro M. Varani Patricia Siguier Michael Chandler John P. Dekker Fred Dyda Insertion Sequence IS<italic toggle="yes">26</italic> Reorganizes Plasmids in Clinically Isolated Multidrug-Resistant Bacteria by Replicative Transposition
description	ABSTRACT Carbapenemase-producing Enterobacteriaceae (CPE), which are resistant to most or all known antibiotics, constitute a global threat to public health. Transposable elements are often associated with antibiotic resistance determinants, suggesting a role in the emergence of resistance. One insertion sequence, IS26, is frequently associated with resistance determinants, but its role remains unclear. We have analyzed the genomic contexts of 70 IS26 copies in several clinical and surveillance CPE isolates from the National Institutes of Health Clinical Center. We used target site duplications and their patterns as guides and found that a large fraction of plasmid reorganizations result from IS26 replicative transpositions, including replicon fusions, DNA inversions, and deletions. Replicative transposition could also be inferred for transposon Tn4401, which harbors the carbapenemase blaKPC gene. Thus, replicative transposition is important in the ongoing reorganization of plasmids carrying multidrug-resistant determinants, an observation that carries substantial clinical and epidemiological implications for understanding how such extreme drug resistance phenotypes evolve. IMPORTANCE Although IS26 is frequently reported to reside in resistance plasmids of clinical isolates, the characteristic hallmark of transposition, target site duplication (TSD), is generally not observed, raising questions about the mode of transposition for IS26. The previous observation of cointegrate formation during transposition implies that IS26 transposes via a replicative mechanism. The other possible outcome of replicative transposition is DNA inversion or deletion, when transposition occurs intramolecularly, and this would also generate a specific TSD pattern that might also serve as supporting evidence for the transposition mechanism. The numerous examples we present here demonstrate that replicative transposition, used by many mobile elements (including IS26 and Tn4401), is prevalent in the plasmids of clinical isolates and results in significant plasmid reorganization. This study also provides a method to trace the evolution of resistance plasmids based on TSD patterns.
format	article
author	Susu He Alison Burgess Hickman Alessandro M. Varani Patricia Siguier Michael Chandler John P. Dekker Fred Dyda
author_facet	Susu He Alison Burgess Hickman Alessandro M. Varani Patricia Siguier Michael Chandler John P. Dekker Fred Dyda
author_sort	Susu He
title	Insertion Sequence IS<italic toggle="yes">26</italic> Reorganizes Plasmids in Clinically Isolated Multidrug-Resistant Bacteria by Replicative Transposition
title_short	Insertion Sequence IS<italic toggle="yes">26</italic> Reorganizes Plasmids in Clinically Isolated Multidrug-Resistant Bacteria by Replicative Transposition
title_full	Insertion Sequence IS<italic toggle="yes">26</italic> Reorganizes Plasmids in Clinically Isolated Multidrug-Resistant Bacteria by Replicative Transposition
title_fullStr	Insertion Sequence IS<italic toggle="yes">26</italic> Reorganizes Plasmids in Clinically Isolated Multidrug-Resistant Bacteria by Replicative Transposition
title_full_unstemmed	Insertion Sequence IS<italic toggle="yes">26</italic> Reorganizes Plasmids in Clinically Isolated Multidrug-Resistant Bacteria by Replicative Transposition
title_sort	insertion sequence is<italic toggle="yes">26</italic> reorganizes plasmids in clinically isolated multidrug-resistant bacteria by replicative transposition
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/4ada9d4fb9c148a89c22b1e6e88a328c
work_keys_str_mv	AT susuhe insertionsequenceisitalictoggleyes26italicreorganizesplasmidsinclinicallyisolatedmultidrugresistantbacteriabyreplicativetransposition AT alisonburgesshickman insertionsequenceisitalictoggleyes26italicreorganizesplasmidsinclinicallyisolatedmultidrugresistantbacteriabyreplicativetransposition AT alessandromvarani insertionsequenceisitalictoggleyes26italicreorganizesplasmidsinclinicallyisolatedmultidrugresistantbacteriabyreplicativetransposition AT patriciasiguier insertionsequenceisitalictoggleyes26italicreorganizesplasmidsinclinicallyisolatedmultidrugresistantbacteriabyreplicativetransposition AT michaelchandler insertionsequenceisitalictoggleyes26italicreorganizesplasmidsinclinicallyisolatedmultidrugresistantbacteriabyreplicativetransposition AT johnpdekker insertionsequenceisitalictoggleyes26italicreorganizesplasmidsinclinicallyisolatedmultidrugresistantbacteriabyreplicativetransposition AT freddyda insertionsequenceisitalictoggleyes26italicreorganizesplasmidsinclinicallyisolatedmultidrugresistantbacteriabyreplicativetransposition
_version_	1718427515407564800

Insertion Sequence IS<italic toggle="yes">26</italic> Reorganizes Plasmids in Clinically Isolated Multidrug-Resistant Bacteria by Replicative Transposition

Ejemplares similares