Journal article

Genetic and biochemical characterization of FRI-1, a carbapenem-hydrolyzing class A β-Lactamase from Enterobacter cloacae

  • Dortet, Laurent Associated National Reference Center for Antibiotic Resistance, Le Kremlin-Bicêtre, France - Faculty of Medicine, South Paris University, Le Kremlin-Bicêtre, France - Bacteriology-Hygiene Unit, Hospital Bicêtre, Assistance Publique/Hôpitaux de Paris, and INSERM U914, Le Kremlin-Bicêtre, France
  • Poirel, Laurent Associated National Reference Center for Antibiotic Resistance, Le Kremlin-Bicêtre, France - Faculty of Medicine, South Paris University, Le Kremlin-Bicêtre, France - Bacteriology-Hygiene Unit, Hospital Bicêtre, Assistance Publique/Hôpitaux de Paris, and INSERM U914, Le Kremlin-Bicêtre, France - Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Department of Medicine, University of Fribourg, Switzerland
  • Abbas, Samia Faculty of Medicine, South Paris University, Le Kremlin-Bicêtre, France
  • Oueslati, Saoussen Faculty of Medicine, South Paris University, Le Kremlin-Bicêtre, France
  • Nordmann, Patrice Associated National Reference Center for Antibiotic Resistance, Le Kremlin-Bicêtre, France - Faculty of Medicine, South Paris University, Le Kremlin-Bicêtre, France - Bacteriology-Hygiene Unit, Hospital Bicêtre, Assistance Publique/Hôpitaux de Paris, and INSERM U914, Le Kremlin-Bicêtre, France - Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Department of Medicine, University of Fribourg, Switzerland - HFR-Hôpital Cantonal, Fribourg, Switzerland
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    12.01.2015
Published in:
  • Antimicrobial Agents and Chemotherapy. - 2016, vol. 59, no. 12, p. 7420–7425
English An Enterobacter cloacae isolate was recovered from a rectal swab from a patient hospitalized in France with previous travel to Switzerland. It was resistant to penicillins, narrow- and broad-spectrum cephalosporins, aztreonam, and carbapenems but remained susceptible to expanded-spectrum cephalosporins. Whereas PCR-based identification of the most common carbapenemase genes failed, the biochemical Carba NP test II identified an Ambler class A carbapenemase. Cloning experiments followed by sequencing identified a gene encoding a totally novel class A carbapenemase, FRI- 1, sharing 51 to 55% amino acid sequence identity with the closest carbapenemase sequences. However, it shared conserved residues as a source of carbapenemase activity. Purified β-lactamase FRI-1 hydrolyzed penicillins, aztreonam, and carbapenems but spared expanded-spectrum cephalosporins. The 50% inhibitory concentrations (IC₅₀s) of clavulanic acid and tazobactam were 10-fold higher than those found for Klebsiella pneumoniae carbapenemase (KPC), IMI, and SME, leading to lower sensitivity of FRI-1 activity to β-lactamase inhibitors. The bla FRI-1 gene was located on a ca. 110-kb untypeable, transferable, and non-self-conjugative plasmid. A putative LysR family regulator-encoding gene at the 5′ end of the β-lactamase gene was identified, leading to inducible expression of the blaFRI-1 gene.
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/305014
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