The role of low molecular weight thiols in Mycobacterium tuberculosis

• Published in: Tuberculosis (Edinburgh, Scotland) Vol. 116; pp. 44 - 55
• Main Authors: Sao Emani, C., Gallant, J.L., Wiid, I.J., Baker, B.
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01.05.2019; Elsevier Science Ltd
• Subjects: Acidic oxides; Animals; Antitubercular Agents - therapeutic use; Biosynthesis; Cellular stress response; Cysteine - metabolism; Damage prevention; Deoxyribonucleic acid; Dipeptides - metabolism; DNA; Drug development; Drug targets; Enzyme Inhibitors - therapeutic use; Enzymes - metabolism; ERG; Ergothioneine - metabolism; Eukaryotes; Free radicals; g-Glutamylcysteine; GGC; Glycopeptides - metabolism; Humans; Immune system; Immunosuppressive agents; Inositol - metabolism; LMW thiols; Low molecular weights; Mechanistic roles; Molecular Targeted Therapy; Molecular Weight; MSH; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - metabolism; Mycobacterium tuberculosis - pathogenicity; Mycothiol; Physiology; Prokaryotes; Reactive nitrogen species; Reactive oxygen species; Roles; Sulfhydryl Compounds - metabolism; Thiols; Tuberculosis; Tuberculosis - drug therapy; Tuberculosis - microbiology; GGC; MSH; ERG; Drug targets; Mechanistic roles; LMW thiols
• ISSN: 1472-9792; 1873-281X
• DOI: 10.1016/j.tube.2019.04.003

Low molecular weight (LMW) thiols are molecules with a functional sulfhydryl group that enable them to detoxify reactive oxygen species, reactive nitrogen species and other free radicals. Their roles range from their ability to modulate the immune system to their ability to prevent damage of biological molecules such as DNA and proteins by protecting against oxidative, nitrosative and acidic stress. LMW thiols are synthesized and found in both eukaryotes and prokaryotes. Due to their beneficial role to both eukaryotes and prokaryotes, their specific functions need to be elucidated, most especially in pathogenic prokaryotes such as Mycobacterium tuberculosis (M.tb), in order to provide a rationale for targeting their biosynthesis for drug development. Ergothioneine (ERG), mycothiol (MSH) and gamma-glutamylcysteine (GGC) are LMW thiols that have been shown to interplay to protect M.tb against cellular stress. Though ERG, MSH and GGC seem to have overlapping functions, studies are gradually revealing their unique physiological roles. Understanding their unique physiological role during the course of tuberculosis (TB) infection, would pave the way for the development of drugs that target their biosynthetic pathway. This review identifies the knowledge gap in the unique physiological roles of LMW thiols and proposes their mechanistic roles based on previous studies. In addition, it gives an update on identified inhibitors of their biosynthetic enzymes.