Institut d'Investigació Sanitària Illes Balears (IdISBa) Research Group.

Biochemical Insights into Imipenem Collateral Susceptibility Driven by ampC Mutations Conferring Ceftolozane/Tazobactam Resistance in Pseudomonas aeruginosa

Gabriel Cabot 1, Kihun Kim 2, Brian L. Mark 2, Antonio Oliver1, Mazdak Khajehpour 3

1Research Unit, University Hospital Son Espases – Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain.
2Department of Microbiology, University of Manitoba, Winnipeg, Canada.
3Department of Chemistry, University of Manitoba, Winnipeg, Canada.

Several Pseudomonas aeruginosa AmpC mutants have emerged that exhibit enhanced activity against ceftazidime and ceftolozane, while also evading inhibition by avibactam. Interestingly, P. aeruginosa strains harboring these AmpC mutations fortuitously exhibit enhanced carbapenem susceptibility. This acquired susceptibility was investigated by comparing the degradation of imipenem by wild-type and cephalosporin-resistant AmpC. We show that cephalosporin-resistant AmpC enzymes lose their efficacy for hydrolyzing imipenem and suggest that this may be due to their increased flexibility and dynamics relative to the wild type.

Antimicrob Agents and Chemoter. 2023 Feb 16; 67(2):e0140922. doi: 10.1128/aac.01409-22.

Link to Antimicrob Agents and Chemoter

Categorised in: Latest publication updates, Uncategorized

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Dr. Bartolome Moyà

Instituto de Investigación Sanitaria Illes Balears

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