Mycothiol: a target for potentiation of rifampin and other antibiotics againstMycobacterium tuberculosis

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.