title: Mycothiol: a target for potentiation of rifampin and other antibiotics against Mycobacterium tuberculosis.
abstract: Actinomycetes, including Mycobacterium species, are Gram-positive bacteria that use the small molecule mycothiol (MSH) as their primary reducing agent and in the detoxification of xenobiotics. Due to these important functions, MSH is a potential target for the development of antibiotics for the treatment of tuberculosis. This review summarizes the progress to date on the viability of enzymes involved in MSH biosynthesis and MSH-dependent detoxification as drug targets, biochemical characterization of target enzymes (structure, mechanism and substrate specificity) and development of MSH biosynthesis and MSH-dependent detoxification enzyme inhibitors. In addition, the ability of MSH to influence the sensitivity of mycobacteria to existing antibiotics and potential of MSH biosynthesis and MSH-dependent detoxification enzyme inhibitors to modulate the activity of existing antibiotics are described.
authors: Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. hernickm@vt.edu
authors: Marcy
authors: M
authors: Hernick
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000494:pharmacology; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry; D006020:Glycopeptides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007294:Inositol / Q000737:chemistry / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology; D012293:Rifampin / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D004791:Enzyme Inhibitors; D006020:Glycopeptides; C089265:mycothiol; D007294:Inositol; D003545:Cysteine; D012293:Rifampin