Two Mutations Commonly Associated with Daptomycin Resistance in Enterococcus faecium LiaS^T120A and LiaR^W73C Appear To Function Epistatically in LiaFSR Signaling.

ABSTRACT: The cyclic antimicrobial lipopeptide daptomycin is now frequently used as a first-line therapy in serious infections caused by multidrug-resistant Enterococcus faecium. Resistance to daptomycin in E. faecium is mediated by activation of the LiaFSR membrane stress response pathway. Deletion of liaR, encoding the response regulator of the system, restores susceptibility to daptomycin, suggesting that the LiaFSR pathway is a potential target for the development of drugs that would induce hypersusceptibility to daptomycin and make it more difficult for enterococci to become daptomycin-resistant. In clinical isolates of E. faecium, substitutions in the membrane-bound histidine kinase LiaS (T120A) and its response regulator LiaR (W73C) are found together, suggesting a potential epistatic relatio

SUBMITTER: Davlieva M 

PROVIDER: S-EPMC7192238 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature