Mycobacterium Tuberculosis Is Extraordinarily Sensitive to Killing by a Vitamin C-induced Fenton Reaction

Nat Commun. 2013;4:1881. doi: 10.1038/ncomms2898.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antitubercular Agents / pharmacology
  • Ascorbic Acid / pharmacology*
  • Cysteine / deficiency
  • DNA Damage
  • Drug Resistance, Bacterial / drug effects
  • Glycopeptides / deficiency
  • Hydrogen Peroxide / metabolism*
  • Inositol / deficiency
  • Iron / metabolism*
  • Lipids / biosynthesis
  • Microbial Sensitivity Tests
  • Microbial Viability / drug effects*
  • Models, Biological
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / genetics
  • Oxidants / pharmacology
  • Reactive Oxygen Species / metabolism
  • Sterilization
  • Transcription, Genetic / drug effects

Substances

  • Antitubercular Agents
  • Fenton's reagent
  • Glycopeptides
  • Lipids
  • Oxidants
  • Reactive Oxygen Species
  • mycothiol
  • Inositol
  • Hydrogen Peroxide
  • Iron
  • Cysteine
  • Ascorbic Acid

Associated data

  • GEO/GSE42293