The Proteasome of Mycobacterium tuberculosis Is Required for Resistance to Nitric Oxide Academic Article uri icon

Overview

MeSH Major

  • Adenosine Triphosphatases
  • Carrier Proteins
  • Cysteine Endopeptidases
  • Macrophages
  • Multienzyme Complexes
  • Mycobacterium tuberculosis
  • Nitric Oxide

abstract

  • The production of nitric oxide and other reactive nitrogen intermediates (RNI) by macrophages helps to control infection by Mycobacterium tuberculosis (Mtb). However, the protection is imperfect and infection persists. To identify genes that Mtb requires to resist RNI, we screened 10,100 Mtb transposon mutants for hypersusceptibility to acidified nitrite. We found 12 mutants with insertions in seven genes representing six pathways, including the repair of DNA (uvrB) and the synthesis of a flavin cofactor (fbiC). Five mutants had insertions in proteasome-associated genes. An Mtb mutant deficient in a presumptive proteasomal adenosine triphosphatase was attenuated in mice, and exposure to proteasomal protease inhibitors markedly sensitized wild-type Mtb to RNI. Thus, the mycobacterial proteasome serves as a defense against oxidative or nitrosative stress.

publication date

  • December 12, 2003

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1126/science.1091176

PubMed ID

  • 14671303

Additional Document Info

start page

  • 1963

end page

  • 6

volume

  • 302

number

  • 5652