Cefiderocol susceptibility endows hope in treating carbapenem-resistant Pseudomonas aeruginosa: insights from in vitro and in silico evidence.

ABSTRACT: 'High-risk' hypermutable clones of Pseudomonas aeruginosa disseminating extensive drug-resistance (XDR) have raised global health concerns with escalating mortality rates in immunocompromised patients. Mutations in conventional drug-targets under antibiotic stress necessitate structural understanding to formulate sustainable therapeutics. In the present study, the major β-lactam antibiotic target, penicillin-binding protein-3 (PBP3) with mutations F533L and T91A, were identified in carbapenemase-positive P. aeruginosa isolates (n = 6) using whole genome sequencing. Antibiotic susceptibility tests showed susceptibility to cefiderocol (MIC ≤ 4 μg ml^-1) despite pan-β-lactam resistance in the isolates. Both the mutations reduced local intra-chain interactions in

SUBMITTER: Basu S 

PROVIDER: S-EPMC11228942 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature