Dataset Information

Antibiotic Resistance Plasmids Cointegrated into a Megaplasmid Harboring the blaOXA-427 Carbapenemase Gene.

ABSTRACT: OXA-427 is a new class D carbapenemase encountered in different species of Enterobacteriaceae in a Belgian hospital. To study the dispersal of this gene, we performed a comparative analysis of two plasmids containing the blaOXA-427 gene, isolated from a Klebsiella pneumoniae strain and an Enterobacter cloacae complex strain. The two IncA/C2 plasmids containing blaOXA-427 share the same backbone; in the K. pneumoniae strain, however, this plasmid is cointegrated into an IncFIb plasmid, forming a 321-kb megaplasmid with multiple multiresistance regions.

SUBMITTER: Desmet S

PROVIDER: S-EPMC5826099 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Antibiotic Resistance Plasmids Cointegrated into a Megaplasmid Harboring the blaOXA-427 Carbapenemase Gene.

Desmet Stefanie S Nepal Suruchi S van Dijl Jan Maarten JM Van Ranst Marc M Chlebowicz Monika A MA Rossen John W JW Van Houdt Jeroen K J JKJ Maes Piet P Lagrou Katrien K Bathoorn Erik E

Antimicrobial agents and chemotherapy 20180223 3

OXA-427 is a new class D carbapenemase encountered in different species of Enterobacteriaceae in a Belgian hospital. To study the dispersal of this gene, we performed a comparative analysis of two plasmids containing the blaOXA-427 gene, isolated from a Klebsiella pneumoniae strain and an Enterobacter cloacae complex strain. The two IncA/C2 plasmids containing blaOXA-427 share the same backbone; in the K. pneumoniae strain, however, ...[more]

PMID: 29311088

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Project description:The worldwide dissemination of carbapenem-resistant Enterobacteriaceae (CRE) poses a critical human health issue by limiting the range of antibiotics that are usable in the treatment of common bacterial infections. Along with CRE, carbapenem heteroresistance has disseminated worldwide, which is described as different levels of carbapenem resistance within a seemingly isogenic bacterial population. Unstable carbapenem resistance will likely lead to unexpected treatment failure due to the enhanced resistance after initiation of treatment, contradicting antimicrobial susceptibility test results. Porin mutation and tandem amplification of the carbapenemase gene have been reported as mechanisms underlying enhanced carbapenem resistance. In this study, we identified multimerization of plasmids carrying carbapenemase genes, by using Southern blotting, whole-genome sequencing, and quantitative PCR (qPCR) analysis for the CRE isolates obtained in our previous surveillance in Osaka, Japan. Plasmids harboring a carbapenemase gene were multimerized by recA, likely through recombination at two consecutive sets of transposase genes of the IS91 family, thereby producing various plasmids of discrete sizes in a single bacterial cell of an Escherichia coli isolate. This multimerization resulted in increased copy numbers of carbapenemase genes, leading to enhanced gene transcription as well as carbapenem resistance. Prior exposure to meropenem further increased the copy number of carbapenemase genes, readily resulting in enhancement of carbapenem resistance. This mechanism may lead to clinical treatment failure by sifting antimicrobial resistance after the treatment initiation. IMPORTANCE We demonstrated the multimerization of plasmids harboring carbapenemase genes, and multimeric plasmids of various discrete sizes existed in a host bacterial cell of Escherichia coli. Plasmid multimerization along with increased copy numbers of carbapenemase genes resulted in enhanced carbapenemase resistance, which was readily accelerated by an overnight preexposure to meropenem. This mechanism may lead to treatment failure in clinical settings after the initiation of antimicrobial therapy.

Dataset Information

Antibiotic Resistance Plasmids Cointegrated into a Megaplasmid Harboring the blaOXA-427 Carbapenemase Gene.

Publications

Antibiotic Resistance Plasmids Cointegrated into a Megaplasmid Harboring the <i>bla</i><sub>OXA-427</sub> Carbapenemase Gene.

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