Journal article

Genetic and biochemical characterization of OXA-405, an OXA-48-Type extended-spectrum β-lactamase without significant carbapenemase activity

  • Dortet, Laurent INSERM U 914, Le Kremlin-Bicêtre, France - Associated National Reference Center for Antibiotic Resistance, Le Kremlin-Bicêtre, France - Faculty of Medicine, South-Paris University, Le Kremlin-Bicêtre, France - Bacteriology-Hygiene Unit, Bicêtre Hospital, Assistance Publique/Hôpitaux de Paris, Le Kremlin-Bicêtre, France
  • Oueslati, Saoussen INSERM U 914, Le Kremlin-Bicêtre, France
  • Jeannot, Katy Associated National Reference Center for Antibiotic Resistance, Le Kremlin-Bicêtre, France - Besançon Hospital, Microbiology Laboratory, Besançon, France
  • Tandé, Didier Brest Hospital, Microbiology Laboratory, Brest, France
  • Naas, Thierry INSERM U 914, Le Kremlin-Bicêtre, France - Associated National Reference Center for Antibiotic Resistance, Le Kremlin-Bicêtre, France - Faculty of Medicine, South-Paris University, Le Kremlin-Bicêtre, France - Bacteriology-Hygiene Unit, Bicêtre Hospital, Assistance Publique/Hôpitaux de Paris, Le Kremlin-Bicêtre, France
  • Nordmann, Patrice INSERM U 914, Le Kremlin-Bicêtre, France - Associated National Reference Center for Antibiotic Resistance, Le Kremlin-Bicêtre, France - Microbiology Unit, Department of Medicine, University Fribourg, Switzerland - HFR-Hôpital Cantonal, Fribourg, Switzerland
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    07.01.2015
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  • Antimicrobial Agents and Chemotherapy. - 2015, vol. 59, no. 7, p. 3823–3828
English The epidemiology of carbapenemases worldwide is showing that OXA-48 variants are becoming the predominant carbapenemase type in Enterobacteriaceae in many countries. However, not all OXA-48 variants possess significant activity toward carbapenems (e.g., OXA-163). Two Serratia marcescens isolates with resistance either to carbapenems or to extended-spectrum cephalosporins were successively recovered from the same patient. A genomic comparison using pulsed-field gel electrophoresis and automated Rep-PCR typing identified a 97.8% similarity between the two isolates. Both strains were resistant to penicillins and first-generation cephalosporins. The first isolate was susceptible to expanded-spectrum cephalosporins, was resistant to carbapenems, and had a significant carbapenemase activity (positive Carba NP test) related to the expression of OXA-48. The second isolate was resistant to expanded-spectrum cephalosporins, was susceptible to carbapenems, and did not express a significant imipenemase activity, (negative for the Carba NP test) despite possessing a blaOXA-48-type gene. Sequencing identified a novel OXA-48-type β-lactamase, OXA-405, with a four-amino-acid deletion compared to OXA-48. The blaOXA-405 gene was located on a ca. 46-kb plasmid identical to the prototype IncL/M blaOXA-48-carrying plasmid except for a ca. 16.4-kb deletion in the tra operon, leading to the suppression of self-conjugation properties. Biochemical analysis showed that OXA-405 has clavulanic acid-inhibited activity toward expanded-spectrum activity without significant imipenemase activity. This is the first identification of a successive switch of catalytic activity in OXA-48-like β-lactamases, suggesting their plasticity. Therefore, this report suggests that the first-line screening of carbapenemase producers in Enterobacteriaceae may be based on the biochemical detection of carbapenemase activity in clinical settings.
Faculty
Faculté des sciences et de médecine
Department
Médecine 3ème année
Language
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/304151
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