noxR3, a novel gene from Mycobacterium tuberculosis, protects Salmonella typhimurium from nitrosative and oxidative stress.

TitlenoxR3, a novel gene from Mycobacterium tuberculosis, protects Salmonella typhimurium from nitrosative and oxidative stress.
Publication TypeJournal Article
Year of Publication1999
AuthorsRuan J, St John G, Ehrt S, Riley L, Nathan C
JournalInfect Immun
Volume67
Issue7
Pagination3276-83
Date Published1999 Jul
ISSN0019-9567
KeywordsAmino Acid Sequence, Bacterial Proteins, Base Sequence, Cloning, Molecular, Gene Expression Regulation, Bacterial, Genes, Bacterial, Molecular Sequence Data, Mycobacterium tuberculosis, Nitrogen Oxides, Oxidative Stress, Reactive Oxygen Species, Salmonella typhimurium
Abstract

Reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) produced by activated macrophages participate in host defense against the facultative intracellular pathogens Mycobacterium tuberculosis and Salmonella typhimurium. To survive within macrophages, such pathogens may have evolved ROI and RNI resistance mechanisms. ROI resistance pathways have been intensively studied. Much less is known about the mechanisms of resistance to RNI. To identify possible RNI resistance genes in M. tuberculosis, a mycobacterial library was expressed in S. typhimurium and subjected to selection by exposure to the NO donor S-nitrosoglutathione (GSNO) in concentrations sufficient to kill the vast majority of nontransformed salmonellae. Among the rare surviving recombinants was a clone expressing noxR3, a novel and previously anonymous M. tuberculosis gene predicted to encode a small, basic protein. Expression of noxR3 protected S. typhimurium not only from GSNO and acidified nitrite but also from H2O2. noxR3 is the third gene cloned from M. tuberculosis that has been shown to protect heterologous cells from both RNI and ROI. This suggests diversity in the repertoire of mechanisms that help pathogens resist the oxidative and nitrosative defenses of the host.

DOI10.1128/IAI.67.7.3276-3283.1999
Alternate JournalInfect Immun
PubMed ID10377101
PubMed Central IDPMC116506
Grant ListT32 GM007739 / GM / NIGMS NIH HHS / United States
GM07739 / GM / NIGMS NIH HHS / United States
HL51967 / HL / NHLBI NIH HHS / United States

Weill Cornell Medicine Microbiology and Immunology 1300 York Avenue, Box 62 New York, NY 10065 Phone: (212) 746-6505 Fax: (212) 746-8587