Rational Design of Potent Activators and Inhibitors of the Enterococcus faecalis Fsr Quorum Sensing Circuit.

ABSTRACT: The increasing rate of resistance development to conventional antibiotics by bacteria necessitates the identification of alternative treatment possibilities that can reduce the ability of bacteria to adapt. Enterococcus faecalis remains the leading cause of clinical enterococci infections and has exhibited quorum sensing (QS)-dependent pathogenicity. Here, we report the development of macrocyclic peptide-based activators and inhibitors of the E. faecalis Fsr QS circuitry. To this end, we developed, optimized, and compared three synthetic routes for lactone-containing macrocyclic peptide scaffolds. We then utilized previous and current structure-activity relationship (SAR) insights of the native QS signaling peptide to rationally design the most potent activators and inhibitors of the Fsr Q

SUBMITTER: McBrayer DN 

PROVIDER: S-EPMC6150820 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature