title: Mycobacterium tuberculosis is extraordinarily sensitive to killing by a vitamin C-induced Fenton reaction.
abstract: Drugs that kill tuberculosis more quickly could shorten chemotherapy significantly. In Escherichia coli, a common mechanism of cell death by bactericidal antibiotics involves the generation of highly reactive hydroxyl radicals via the Fenton reaction. Here we show that vitamin C, a compound known to drive the Fenton reaction, sterilizes cultures of drug-susceptible and drug-resistant Mycobacterium tuberculosis, the causative agent of tuberculosis. While M. tuberculosis is highly susceptible to killing by vitamin C, other Gram-positive and Gram-negative pathogens are not. The bactericidal activity of vitamin C against M. tuberculosis is dependent on high ferrous ion levels and reactive oxygen species production, and causes a pleiotropic effect affecting several biological processes. This study enlightens the possible benefits of adding vitamin C to an anti-tuberculosis regimen and suggests that the development of drugs that generate high oxidative burst could be of great use in tuberculosis treatment.
authors.affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx, New York 10461, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Vilchèze
authors.forename: Travis
authors.initials: T
authors.lastname: Hartman
authors.forename: Brian
authors.initials: B
authors.lastname: Weinrick
authors.forename: William R
authors.initials: WR
authors.lastname: Jacobs
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology*; D003545:Cysteine / Q000172:deficiency; D004249:DNA Damage; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D006020:Glycopeptides / Q000172:deficiency; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007294:Inositol / Q000172:deficiency; D007501:Iron / Q000378:metabolism*; D008055:Lipids / Q000096:biosynthesis; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects*; D008954:Models, Biological; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D016877:Oxidants / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013242:Sterilization; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000995:Antitubercular Agents; C045076:Fenton's reagent; D006020:Glycopeptides; D008055:Lipids; D016877:Oxidants; D017382:Reactive Oxygen Species; C089265:mycothiol; D007294:Inositol; D006861:Hydrogen Peroxide; D007501:Iron; D003545:Cysteine; D001205:Ascorbic Acid