Structural basis of Pseudomonas aeruginosa penicillin binding protein 3 inhibition by the siderophore-antibiotic cefiderocol.

ABSTRACT: The breakthrough cephalosporin cefiderocol, approved for clinical use in 2019, has activity against many Gram-negative bacteria. The catechol group of cefiderocol enables it to efficiently enter bacterial cells via the iron/siderophore transport system thereby reducing resistance due to porin channel mutations and efflux pump upregulation. Limited information is reported regarding the binding of cefiderocol to its key proposed target, the transpeptidase penicillin binding protein 3 (PBP3). We report studies on the reaction of cefiderocol and the related cephalosporins ceftazidime and cefepime with Pseudomonas aeruginosa PBP3, including inhibition measurements, protein observed mass spectrometry, and X-ray crystallography. The three cephalosporins form analogous 3-exomethylene

SUBMITTER: Smith HG 

PROVIDER: S-EPMC11423509 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature