Mutations in mmpL and in the cell wall stress stimulon contribute to resistance to oxadiazole antibiotics in methicillin-resistant Staphylococcus aureus.

ABSTRACT: Staphylococcus aureus is a leading cause of hospital- and community-acquired infections, which exhibit broad resistance to various antibiotics. We recently disclosed the discovery of the oxadiazole class of antibiotics, which has in vitro and in vivo activities against methicillin-resistant S. aureus (MRSA). We report herein that MmpL, a putative member of the resistance, nodulation, and cell division (RND) family of proteins, contributes to oxadiazole resistance in the S. aureus strain COL. Through serial passages, we generated two S. aureus COL variants that showed diminished susceptibilities to an oxadiazole antibiotic. The MICs for the oxadiazole against one strain (designated S. aureus COL(I)) increased reproducibly 2-fold (to 4 μg/ml), while against the other strain (S. aureus COL(R)

SUBMITTER: Xiao Q 

PROVIDER: S-EPMC4187926 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature