Gut Microbiota Metabolite Indole Propionic Acid Targets Tryptophan Biosynthesis in Mycobacterium tuberculosis.

ABSTRACT: Indole propionic acid (IPA), produced by the gut microbiota, is active against Mycobacterium tuberculosisin vitro and in vivo However, its mechanism of action is unknown. IPA is the deamination product of tryptophan (Trp) and thus a close structural analog of this essential aromatic amino acid. De novo Trp biosynthesis in M. tuberculosis is regulated through feedback inhibition: Trp acts as an allosteric inhibitor of anthranilate synthase TrpE, which catalyzes the first committed step in the Trp biosynthesis pathway. Hence, we hypothesized that IPA may mimic Trp as an allosteric inhibitor of TrpE and exert its antimicrobial effect by blocking synthesis of Trp at the TrpE catalytic step. To test our hypothesis, we carried out metabolic, chemical rescue, ge

SUBMITTER: Negatu DA 

PROVIDER: S-EPMC6437058 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature