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Mechanisms of Resistance

Genetic Features Leading to Reduced Susceptibility to Aztreonam-Avibactam among Metallo-β-Lactamase-Producing Escherichia coli Isolates

Mustafa Sadek, Mario Juhas, Laurent Poirel, Patrice Nordmann
Mustafa Sadek
aMedical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
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Mario Juhas
aMedical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
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Laurent Poirel
aMedical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
bSwiss National Reference Center for Emerging Antibiotic Resistance (NARA), University of Fribourg, Fribourg, Switzerland
cINSERM European Unit (IAME, France), University of Fribourg, Fribourg, Switzerland
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Patrice Nordmann
aMedical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
bSwiss National Reference Center for Emerging Antibiotic Resistance (NARA), University of Fribourg, Fribourg, Switzerland
cINSERM European Unit (IAME, France), University of Fribourg, Fribourg, Switzerland
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DOI: 10.1128/AAC.01659-20
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ABSTRACT

Metallo-β-lactamase (MBL)-producing Escherichia coli isolates resistant to the newly developed β-lactam/β-lactamase inhibitor drug combination aztreonam-avibactam (ATM-AVI) have been reported. Here, we analyzed a series of 118 clinical MBL-producing E. coli isolates of various geographical origins for susceptibility to ATM-AVI. The nature of the PBP3 protein sequence and the occurrence of blaCMY genes for susceptibility to ATM-AVI were investigated. We showed here that elevated MICs of ATM-AVI among MBL-producing E. coli isolates resulted from a combination of different features, including modification of PBP3 protein sequence through specific amino acid insertions and production of CMY-type enzymes, particularly, CMY-42. We showed here that those insertions identified in the PBP3 sequence are not considered the unique basis of resistance to ATM-AVI, but they significantly contribute to it.

FOOTNOTES

    • Received 30 July 2020.
    • Returned for modification 10 September 2020.
    • Accepted 24 September 2020.
    • Accepted manuscript posted online 28 September 2020.
  • Supplemental material is available online only.

  • Copyright © 2020 American Society for Microbiology.

All Rights Reserved.

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Genetic Features Leading to Reduced Susceptibility to Aztreonam-Avibactam among Metallo-β-Lactamase-Producing Escherichia coli Isolates
Mustafa Sadek, Mario Juhas, Laurent Poirel, Patrice Nordmann
Antimicrobial Agents and Chemotherapy Nov 2020, 64 (12) e01659-20; DOI: 10.1128/AAC.01659-20

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Genetic Features Leading to Reduced Susceptibility to Aztreonam-Avibactam among Metallo-β-Lactamase-Producing Escherichia coli Isolates
Mustafa Sadek, Mario Juhas, Laurent Poirel, Patrice Nordmann
Antimicrobial Agents and Chemotherapy Nov 2020, 64 (12) e01659-20; DOI: 10.1128/AAC.01659-20
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KEYWORDS

Escherichia coli
aztreonam-avibactam
metallo-β-lactamase
PBP3
NDM
CMY-42

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