FabH mutations confer resistance to FabF-directed antibiotics in Staphylococcus aureus.

ABSTRACT: Delineating the mechanisms for genetically acquired antibiotic resistance is a robust approach to target validation and anticipates the evolution of clinical drug resistance. This study defines a spectrum of mutations in fabH that render Staphylococcus aureus resistant to multiple natural products known to inhibit the elongation condensing enzyme (FabF) of bacterial type II fatty acid synthesis. Twenty independently isolated clones resistant to platensimycin, platencin, or thiolactomycin were isolated. All mutants selected against one antibiotic were cross-resistant to the other two antibiotics. Mutations were not detected in fabF, but the resistant strains harbored missense mutations in fabH. The altered amino acids clustered in and around the FabH active-site tunnel. The mutant FabH prot

SUBMITTER: Parsons JB 

PROVIDER: S-EPMC4335864 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature