Discovery of uncompetitive inhibitors of SapM that compromise intracellular survival of Mycobacterium tuberculosis.

ABSTRACT: SapM is a secreted virulence factor from Mycobacterium tuberculosis critical for pathogen survival and persistence inside the host. Its full potential as a target for tuberculosis treatment has not yet been exploited because of the lack of potent inhibitors available. By screening over 1500 small molecules, we have identified new potent and selective inhibitors of SapM with an uncompetitive mechanism of inhibition. The best inhibitors share a trihydroxy-benzene moiety essential for activity. Importantly, the inhibitors significantly reduce mycobacterial burden in infected human macrophages at 1 µM, and they are selective with respect to other mycobacterial and human phosphatases. The best inhibitor also reduces intracellular burden of Francisella tularensis, which secretes the virulence fa

SUBMITTER: Fernandez-Soto P 

PROVIDER: S-EPMC8027839 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature