The ESX-3 secretion system is necessary for iron and zinc homeostasis in Mycobacterium tuberculosis

PLoS One. 2013 Oct 14;8(10):e78351. doi: 10.1371/journal.pone.0078351. eCollection 2013.

Abstract

ESX-3 is one of the five type VII secretion systems encoded by the Mycobacterium tuberculosis genome. We recently showed the essentiality of ESX-3 for M. tuberculosis viability and proposed its involvement in iron and zinc metabolism. In this study we confirmed the role of ESX-3 in iron uptake and its involvement in the adaptation to low zinc environment in M. tuberculosis. Moreover, we unveiled functional differences between the ESX-3 roles in M. tuberculosis and M. smegmatis showing that in the latter ESX-3 is only involved in the adaptation to iron and not to zinc restriction. Finally, we also showed that in M. tuberculosis this secretion system is essential for iron and zinc homeostasis not only in conditions in which the concentrations of these metals are limiting but also in metal sufficient conditions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / metabolism*
  • Bacterial Secretion Systems* / drug effects
  • Cell Line
  • Cell Wall / drug effects
  • Cell Wall / metabolism
  • Gene Expression Regulation, Bacterial / drug effects
  • Genes, Bacterial / genetics
  • Hemin / pharmacology
  • Homeostasis* / drug effects
  • Humans
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Iron / metabolism*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Mutation / genetics
  • Mycobacterium smegmatis / drug effects
  • Mycobacterium smegmatis / metabolism
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / growth & development
  • Mycobacterium tuberculosis / metabolism*
  • Oxazoles / metabolism
  • Permeability / drug effects
  • Streptonigrin / pharmacology
  • Transcription, Genetic / drug effects
  • Zinc / metabolism*

Substances

  • Bacterial Proteins
  • Bacterial Secretion Systems
  • Oxazoles
  • Streptonigrin
  • Hemin
  • Iron
  • Zinc