Rifamycin congeners kanglemycins are active against rifampicin-resistant bacteria via a distinct mechanism.

ABSTRACT: Rifamycin antibiotics (Rifs) target bacterial RNA polymerases (RNAPs) and are widely used to treat infections including tuberculosis. The utility of these compounds is threatened by the increasing incidence of resistance (Rif^R). As resistance mechanisms found in clinical settings may also occur in natural environments, here we postulated that bacteria could have evolved to produce rifamycin congeners active against clinically relevant resistance phenotypes. We survey soil metagenomes and identify a tailoring enzyme-rich family of gene clusters encoding biosynthesis of rifamycin congeners (kanglemycins, Kangs) with potent in vivo and in vitro activity against the most common clinically relevant Rif^R mutations. Our structural and mechanistic analyses reveal the basis fo

SUBMITTER: Peek J 

PROVIDER: S-EPMC6175910 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature