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CTX-M-15-Producing Shewanella Species Clinical Isolate Expressing OXA-535, a Chromosome-Encoded OXA-48 Variant, Putative Progenitor of the Plasmid-Encoded OXA-436.

Abstract
Shewanella spp. constitute a reservoir of antibiotic resistance determinants. In a bile sample, we identified three extended-spectrum-β-lactamase (ESBL)-producing bacteria (Escherichia coli, Klebsiella pneumoniae, and Shewanella sp. strain JAB-1) isolated from a child suffering from cholangitis. Our objectives were to characterize the genome and the resistome of the first ESBL-producing isolate of the genus Shewanella and determine whether plasmidic exchange occurred between the three bacterial species. Bacterial isolates were characterized using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), standard biochemical tools, and antimicrobial susceptibility testing. Shewanella sp. JAB-1 and ESBL gene-encoding plasmids were characterized using PacBio and Illumina whole-genome sequencing, respectively. The Shewanella sp. JAB-1 chromosome-encoded OXA-48 variant was cloned and functionally characterized. Whole-genome sequencing (WGS) of the Shewanella sp. clinical isolate JAB-1 revealed the presence of a 193-kb plasmid belonging to the IncA/C incompatibility group and harboring two ESBL genes, blaCTX-M-15 and blaSHV-2ablaCTX-M-15 gene-carrying plasmids belonging to the IncY and IncR incompatibility groups were also found in the E. coli and K. pneumoniae isolates from the same patient, respectively. A comparison of the blaCTX-M-15 genetic environment indicated the independent origin of these plasmids and dismissed in vivo transfers. Furthermore, characterization of the resistome of Shewanella sp. JAB-1 revealed the presence of a chromosome-carried blaOXA-535 gene, likely the progenitor of the plasmid-carried blaOXA-436 gene, a novel blaOXA-48-like gene. The expression of blaOXA-535 in E. coli showed the carbapenem-hydrolyzing activity of OXA-535. The production of OXA-535 in Shewanella sp. JAB-1 could be evidenced using molecular and immunoenzymatic tests, but not with biochemical tests that monitor carbapenem hydrolysis. In this study, we have identified a CTX-M-15-producing Shewanella species that was responsible for a hepatobiliary infection and that is likely the progenitor of OXA-436, a novel plasmid-encoded OXA-48-like class D carbapenemase.
AuthorsAgnès B Jousset, Laura Dabos, Rémy A Bonnin, Delphine Girlich, Anaïs Potron, Nicolas Cabanel, Laurent Dortet, Philippe Glaser, Thierry Naas
JournalAntimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 62 Issue 1 (01 2018) ISSN: 1098-6596 [Electronic] United States
PMID29038283 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2017 American Society for Microbiology.
Chemical References
  • Anti-Bacterial Agents
  • beta-Lactamases
Topics
  • Anti-Bacterial Agents (pharmacology)
  • Child
  • Cholangitis (microbiology)
  • Cross Infection (drug therapy, microbiology)
  • Escherichia coli (drug effects, genetics)
  • Escherichia coli Infections (drug therapy, microbiology)
  • Female
  • Humans
  • Klebsiella Infections (drug therapy, microbiology)
  • Klebsiella pneumoniae (drug effects, genetics)
  • Plasmids (genetics)
  • Shewanella (drug effects, genetics)
  • beta-Lactamases (genetics)

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