Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 64, Issue 12, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.01659-20
Keywords
Escherichia coli; aztreonam-avibactam; metallo-beta-lactamase; PBP3; NDM; CMY-42
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Funding
- University of Fribourg, Switzerland
- Swiss National Science Foundation [FNS-31003A_163432, FNS-407240_177381]
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Metallo-beta-lactamase (MBL)-producing Escherichia coli isolates resistant to the newly developed beta-lactam/beta-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 bla(CMY) 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.
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