High throughput phenotypic selection of Mycobacterium tuberculosis mutants with impaired resistance to reactive oxygen species identifies genes important for intracellular growth

PLoS One. 2013;8(1):e53486. doi: 10.1371/journal.pone.0053486. Epub 2013 Jan 8.

Abstract

Mycobacterium tuberculosis has the remarkable capacity to survive within the hostile environment of the macrophage, and to resist potent antibacterial molecules such as reactive oxygen species (ROS). Thus, understanding mycobacterial resistance mechanisms against ROS may contribute to the development of new anti-tuberculosis therapies. Here we identified genes involved in such mechanisms by screening a high-density transposon mutant library, and we show that several of them are involved in the intracellular lifestyle of the pathogen. Many of these genes were found to play a part in cell envelope functions, further strengthening the important role of the mycobacterial cell envelope in protection against aggressions such as the ones caused by ROS inside host cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Disease Resistance / genetics
  • Genes, Bacterial / physiology*
  • High-Throughput Screening Assays
  • Host-Pathogen Interactions / genetics
  • Humans
  • Macrophages / metabolism
  • Macrophages / microbiology*
  • Macrophages / pathology
  • Mutation*
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / growth & development*
  • Phenotype*
  • Reactive Oxygen Species / metabolism
  • Reactive Oxygen Species / pharmacology*
  • Tuberculosis, Pulmonary / microbiology
  • Tuberculosis, Pulmonary / pathology
  • Tuberculosis, Pulmonary / prevention & control

Substances

  • Reactive Oxygen Species

Grants and funding

This work was supported by the European NEWTBVAC FP7 241745 Project. OM is a recipient of a Fellowship from Fundação para a Ciência e Tecnologia (SFRH/BD/39079/2007). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.