Inhibition of mycolic acid transport across the Mycobacterium tuberculosis plasma membrane.

ABSTRACT: New chemotherapeutics active against multidrug-resistant Mycobacterium tuberculosis are urgently needed. We report on the identification of an adamantyl urea compound that shows potent bactericidal activity against M. tuberculosis and a unique mode of action, namely the abolition of the translocation of mycolic acids from the cytoplasm, where they are synthesized to the periplasmic side of the plasma membrane and are in turn transferred onto cell wall arabinogalactan or used in the formation of virulence-associated, outer membrane, trehalose-containing glycolipids. Whole-genome sequencing of spontaneous-resistant mutants of M. tuberculosis selected in vitro followed by genetic validation experiments revealed that our prototype inhibitor targets the inner membrane transporter MmpL3. Conditi

SUBMITTER: Grzegorzewicz AE 

PROVIDER: S-EPMC3307863 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature