OXA-427, a new plasmid-borne carbapenem-hydrolysing class D β-lactamase in Enterobacteriaceae

Pierre Bogaerts, Thierry Naas, Veroniek Saegeman, Remy A. Bonnin, Annette Schuermans, Stéphanie Evrard, Warda Bouchahrouf, Thomas Jove, Didier Tande, Xavier de Bolle, Te Din Huang, Laurent Dortet, Youri Glupczynski

Research output: Contribution to journalArticle

Abstract

Objectives: To describe a novel plasmid-borne class D carbapenemase (CHDL) named OXA-427 identified in several Enterobacteriaceae clinical isolates from nine patients in one Belgian hospital. Methods: OXA-427-producing isolates were analysed by an electrochemical imipenem hydrolysis method (BYG Carba test), Carba NP test, conventional phenotypic assays and by molecular methods (PCR, whole sequencing of the OXA-427-encoding plasmid and cloning). The antimicrobial resistance profile of OXA-427 was analysed by expression of the cloned gene in Escherichia coli DH10B and J53. Results: Eleven OXA-427-producing Enterobacteriaceae isolates of various species were identified from clinical specimens of nine patients between March 2012 and June 2014. OXA-427 shares only 22%-29% amino acid identity with OXA-48-like enzymes and other acquired CHDL (e.g. OXA-23, -24/40 and -58 of Acinetobacter spp.). Conversely, it appeared closely related to the chromosomal class D β-lactamase of Aeromonas media, Aeromonas hydrophila and Aeromonas sobria (99%, 89% and 77% of identity, respectively). When expressed in E. coli, OXA-427 hydrolysed imipenem and conferred resistance to extended-spectrum cephalosporins (mostly ceftazidime), penicillins including temocillin, and reduced susceptibility to carbapenems. The blaOXA-427 gene was located in a 45 kb resistance island on a 177 kb IncA/C plasmid. Conclusions: OXA-427 is a novel CHDL most closely related to chromosomal class D β-lactamase of A. media WS. It confers resistance to penicillins, ceftazidime and aztreonam and in some instances to carbapenems. OXA- 427, which is not detectable by classical molecular tests, caused a protracted outbreak in one university hospital over a 2 year period.

Original languageEnglish
Pages (from-to)2469-2477
Number of pages9
JournalThe Journal of antimicrobial chemotherapy
Volume72
Issue number9
DOIs
Publication statusPublished - 1 Sep 2017

Keywords

  • Journal Article
  • Carbapenems/metabolism
  • Humans
  • Middle Aged
  • Drug Resistance, Multiple, Bacterial/genetics
  • Enterobacteriaceae Infections/epidemiology
  • Plasmids/genetics
  • Anti-Bacterial Agents/metabolism
  • Male
  • Escherichia coli/drug effects
  • Enterobacteriaceae/enzymology
  • Hydrolysis
  • Microbial Sensitivity Tests
  • Belgium/epidemiology
  • Bacterial Proteins/genetics
  • Cloning, Molecular
  • High-Throughput Nucleotide Sequencing
  • beta-Lactamases/genetics

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    Bogaerts, P., Naas, T., Saegeman, V., Bonnin, R. A., Schuermans, A., Evrard, S., Bouchahrouf, W., Jove, T., Tande, D., de Bolle, X., Huang, T. D., Dortet, L., & Glupczynski, Y. (2017). OXA-427, a new plasmid-borne carbapenem-hydrolysing class D β-lactamase in Enterobacteriaceae. The Journal of antimicrobial chemotherapy, 72(9), 2469-2477. https://doi.org/10.1093/jac/dkx184