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 of Fribourg, Switzerland - HFR-Hôpital Cantonal, Fribourg, Switzerland
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07.01.2015
Published in:
- 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
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 255896
- DOI 10.1128/AAC.05058-14
- Persistent URL
- https://folia.unifr.ch/unifr/documents/304151
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