Identification of nitric oxide synthase as a protective locus against tuberculosis Academic Article Article uri icon

Overview

MeSH Major

  • Anti-Bacterial Agents
  • Biomedical Research
  • Drug Design
  • Drug Industry
  • Marketing
  • Research Support as Topic

abstract

  • Mutagenesis of the host immune system has helped identify response pathways necessary to combat tuberculosis. Several such pathways may function as activators of a common protective gene: inducible nitric oxide synthase (NOS2). Here we provide direct evidence for this gene controlling primary Mycobacterium tuberculosis infection using mice homozygous for a disrupted NOS2 allele. NOS2(-/-) mice proved highly susceptible, resembling wild-type littermates immunosuppressed by high-dose glucocorticoids, and allowed Mycobacterium tuberculosis to replicate faster in the lungs than reported for other gene-deficient hosts. Susceptibility appeared to be independent of the only known naturally inherited antimicrobial locus, NRAMP1. Progression of chronic tuberculosis in wild-type mice was accelerated by specifically inhibiting NOS2 via administration of N6-(1-iminoethyl)-L-lysine. Together these findings identify NOS2 as a critical host gene for tuberculostasis.

publication date

  • May 13, 1997

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1073/pnas.94.10.5243

PubMed ID

  • 9144222

Additional Document Info

start page

  • 5243

end page

  • 8

volume

  • 94

number

  • 10