Biochemical Insights into Imipenem Collateral Susceptibility Driven by <i>ampC</i> Mutations Conferring Ceftolozane/Tazobactam Resistance in Pseudomonas aeruginosa
Gabriel Cabot, Kihun Kim, Brian L. Mark, Antonio Oliver, Mazdak Khajehpour
Abstract
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.
Topics & Concepts
Pseudomonas aeruginosaImipenemMicrobiologyBiologyTazobactamCollateral damageVirologyMedicineAntibiotic resistanceAntibioticsBacteriaGeneticsSociologyCriminologyAntibiotic Resistance in BacteriaAntibiotics Pharmacokinetics and EfficacyBacterial biofilms and quorum sensing