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Carbapenem triggers dissemination of chromosomally integrated carbapenemase genes via conjugative plasmids in Escherichia coli

Epidemiological surveys have shown that carbapenem resistance is mainly transmitted across species by carbapenemase genes located on conjugative plasmids. As chromosomal integration of carbapenemase genes has rarely been identified, only a few studies have investigated their advantages to the carbap...

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Autores principales: Abe, Ryuichiro, Akeda, Yukihiro, Sugawara, Yo, Matsumoto, Yuki, Motooka, Daisuke, Iida, Tetsuya, Hamada, Shigeyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10308940/
https://www.ncbi.nlm.nih.gov/pubmed/37272726
http://dx.doi.org/10.1128/msystems.01275-22
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author Abe, Ryuichiro
Akeda, Yukihiro
Sugawara, Yo
Matsumoto, Yuki
Motooka, Daisuke
Iida, Tetsuya
Hamada, Shigeyuki
author_facet Abe, Ryuichiro
Akeda, Yukihiro
Sugawara, Yo
Matsumoto, Yuki
Motooka, Daisuke
Iida, Tetsuya
Hamada, Shigeyuki
author_sort Abe, Ryuichiro
collection PubMed
description Epidemiological surveys have shown that carbapenem resistance is mainly transmitted across species by carbapenemase genes located on conjugative plasmids. As chromosomal integration of carbapenemase genes has rarely been identified, only a few studies have investigated their advantages to the carbapenem-resistant bacterial community. Here, we confirmed the increased stability of bla(IMP-6) on a chromosome-integrated plasmid in an Escherichia coli isolate compared with that on original plasmids in the absence of antibiotic pressure. Although plasmids carrying carbapenemase genes are supposedly lost in successive generations, we found that the complete plasmid backbone was retained in bacterial cells even after the occasional loss of their antibiotic-resistance cassettes. This backbone structure has been observed worldwide to carry various antimicrobial resistance genes. Although the chromosomally integrated plasmid carrying bla(IMP-6) could not be transmitted by conjugation, we found that meropenem treatment for 1 wk allowed the plasmid to be released from the chromosome and spread among E. coli strains that were susceptible to meropenem. The copy number of bla(IMP-6) on the plasmid was amplified eight times, resulting in enhanced resistance. Although the carbapenemase producers that carry chromosomal carbapenemase genes comprised of small subpopulations, they functioned as stable, long-term reservoirs of carbapenem resistance that could be disseminated via plasmids with amplified resistance upon meropenem stimulation. Although plasmids occasionally lose their resistance cassettes as a scaffold for the acquisition of another resistance gene, chromosomal integration may contribute to the effective sharing of carbapenem resistance within a population, complicating the development of a strategy to avoid the dissemination of antimicrobial resistance. IMPORTANCE: Although carbapenem antibiotics are the last resort for combating multidrug-resistant organisms, global dissemination of carbapenem-resistant Enterobacteriaceae (CRE) threatens public health. Carbapenemases, which are enzymes responsible for carbapenem resistance, are mainly encoded by genes on plasmids that can be transmitted across bacterial species. Owing to the rarity of chromosomally encoded carbapenemase genes, studies investigating their properties in bacterial communities are lacking. In our study, we revealed the stability of carbapenemase genes on chromosomes compared with those on plasmids, which can be lost through the loss of antimicrobial resistance cassettes despite robust retention of plasmid backbones. Following exposure to meropenem, the carbapenemase gene integrated into the chromosome was released as a plasmid, restarting the dissemination of enhanced carbapenem resistance through amplified copy numbers of carbapenemase genes. Chromosomally encoded carbapenemase genes may function as a reservoir of resistance genes within the bacterial community and challenge infection control against CRE dissemination.
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spelling pubmed-103089402023-06-30 Carbapenem triggers dissemination of chromosomally integrated carbapenemase genes via conjugative plasmids in Escherichia coli Abe, Ryuichiro Akeda, Yukihiro Sugawara, Yo Matsumoto, Yuki Motooka, Daisuke Iida, Tetsuya Hamada, Shigeyuki mSystems Research Article Epidemiological surveys have shown that carbapenem resistance is mainly transmitted across species by carbapenemase genes located on conjugative plasmids. As chromosomal integration of carbapenemase genes has rarely been identified, only a few studies have investigated their advantages to the carbapenem-resistant bacterial community. Here, we confirmed the increased stability of bla(IMP-6) on a chromosome-integrated plasmid in an Escherichia coli isolate compared with that on original plasmids in the absence of antibiotic pressure. Although plasmids carrying carbapenemase genes are supposedly lost in successive generations, we found that the complete plasmid backbone was retained in bacterial cells even after the occasional loss of their antibiotic-resistance cassettes. This backbone structure has been observed worldwide to carry various antimicrobial resistance genes. Although the chromosomally integrated plasmid carrying bla(IMP-6) could not be transmitted by conjugation, we found that meropenem treatment for 1 wk allowed the plasmid to be released from the chromosome and spread among E. coli strains that were susceptible to meropenem. The copy number of bla(IMP-6) on the plasmid was amplified eight times, resulting in enhanced resistance. Although the carbapenemase producers that carry chromosomal carbapenemase genes comprised of small subpopulations, they functioned as stable, long-term reservoirs of carbapenem resistance that could be disseminated via plasmids with amplified resistance upon meropenem stimulation. Although plasmids occasionally lose their resistance cassettes as a scaffold for the acquisition of another resistance gene, chromosomal integration may contribute to the effective sharing of carbapenem resistance within a population, complicating the development of a strategy to avoid the dissemination of antimicrobial resistance. IMPORTANCE: Although carbapenem antibiotics are the last resort for combating multidrug-resistant organisms, global dissemination of carbapenem-resistant Enterobacteriaceae (CRE) threatens public health. Carbapenemases, which are enzymes responsible for carbapenem resistance, are mainly encoded by genes on plasmids that can be transmitted across bacterial species. Owing to the rarity of chromosomally encoded carbapenemase genes, studies investigating their properties in bacterial communities are lacking. In our study, we revealed the stability of carbapenemase genes on chromosomes compared with those on plasmids, which can be lost through the loss of antimicrobial resistance cassettes despite robust retention of plasmid backbones. Following exposure to meropenem, the carbapenemase gene integrated into the chromosome was released as a plasmid, restarting the dissemination of enhanced carbapenem resistance through amplified copy numbers of carbapenemase genes. Chromosomally encoded carbapenemase genes may function as a reservoir of resistance genes within the bacterial community and challenge infection control against CRE dissemination. American Society for Microbiology 2023-06-05 /pmc/articles/PMC10308940/ /pubmed/37272726 http://dx.doi.org/10.1128/msystems.01275-22 Text en Copyright © 2023 Abe et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Abe, Ryuichiro
Akeda, Yukihiro
Sugawara, Yo
Matsumoto, Yuki
Motooka, Daisuke
Iida, Tetsuya
Hamada, Shigeyuki
Carbapenem triggers dissemination of chromosomally integrated carbapenemase genes via conjugative plasmids in Escherichia coli
title Carbapenem triggers dissemination of chromosomally integrated carbapenemase genes via conjugative plasmids in Escherichia coli
title_full Carbapenem triggers dissemination of chromosomally integrated carbapenemase genes via conjugative plasmids in Escherichia coli
title_fullStr Carbapenem triggers dissemination of chromosomally integrated carbapenemase genes via conjugative plasmids in Escherichia coli
title_full_unstemmed Carbapenem triggers dissemination of chromosomally integrated carbapenemase genes via conjugative plasmids in Escherichia coli
title_short Carbapenem triggers dissemination of chromosomally integrated carbapenemase genes via conjugative plasmids in Escherichia coli
title_sort carbapenem triggers dissemination of chromosomally integrated carbapenemase genes via conjugative plasmids in escherichia coli
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10308940/
https://www.ncbi.nlm.nih.gov/pubmed/37272726
http://dx.doi.org/10.1128/msystems.01275-22
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