Death of Mycobacterium tuberculosis by L-arginine starvation

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 115; no. 39; pp. 9658 - 9660
• Main Authors: Mizrahi, Valerie, Warner, Digby F.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 25.09.2018
• Subjects: Antioxidants; Arginine; Biological Sciences; Biosynthesis; Cell death; Commentaries; COMMENTARY; Damage accumulation; Deoxyribonucleic acid; DNA; DNA damage; DNA repair; Flow cytometry; Gene expression; Gene regulation; Mortality; Mutants; Mycobacterium tuberculosis; Oxidative stress; Reactive oxygen species; Supplements; Time dependence; Tuberculosis
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1813587115

Mizrahi et al talk about the Tuberculosis (TB) as currently the leading cause of mortality from a single infectious agent. To explore the physiological basis of the rapid death of Mycobacterium tuberculosis (Mtb) consequent on L-arginine starvation, Tiwari et al turned again to transcriptomics to monitor time-dependent changes in gene expression in the L-arginine--starved mutants over a period of up to 6 d. Those studies give key insights into the nature and extent of the metabolic mayhem unleashed in Mtb upon L-arginine starvation over a period of time in which cell death--as evidenced by a decline in colony-forming units--was already underway. Up-regulation of genes in L-arginine biosynthesis, cell envelope stress and remodeling, oxidative stress and antioxidant defense, Fe-S cluster biogenesis and assembly, and DNA repair was observed in the ▵argB mutant under L-arginine starvation. To examine the association more closely, Tiwari et al used flow cytometry to measure the time-dependent accumulation of ROS and DNA damage in the ▵argB and ▵argF mutants in media with or without L-arginine supplementation.