Ergothioneine Maintains Redox and Bioenergetic Homeostasis Essential for Drug Susceptibility and Virulence of Mycobacterium tuberculosis

• DOI: 10.1016/j.celrep.2015.12.056
• Publication Date: 2016-01-07T18:45:32Z
• Authors: Vikram Saini; Bridgette M. Cumming; Loni Guidry; Dirk A. Lamprecht; John H. Adamson; Vineel P. Reddy; Krishna C. Chinta; James H. Mazorodze; Joel N. Glasgow; Melissa Richard-G...; Anaximandro Gomez...; Horacio Bach; Yossef Av-Gay; Hyungjin Eoh; Kyu Rhee; Adrie J.C. Steyn
• Keywords: Bioenergetics; Homeostasis; Antimycobacterial

Highlights•WhiB3 regulates EGT production and maintains bioenergetic homeostasis in Mtb•EGT modulates drug sensitivity protects Mtb from diverse oxidative stressors•EGT is essential for survival macrophages miceSummaryThe mechanisms by which Mycobacterium tuberculosis (Mtb) metabolic equilibrium to survive during infection upon exposure antimycobacterial drugs are poorly characterized. Ergothioneine (EGT) mycothiol (MSH) the major redox buffers present Mtb, but contribution of virulence remains unknown. We report that WhiB3, a 4Fe-4S sensor protein, homeostasis. show central carbon metabolism lipid precursors regulate sensitivity. Notably, MSH both Transcriptomic analyses mutants indicate overlapping distinct functions MSH. Last, we critical mice. This study has uncovered dynamic balance between homeostasis, critically influences susceptibility pathogenicity.Graphical abstract