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PMID: 9382887 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A novel antioxidant gene from Mycobacterium tuberculosis.

The Journal of experimental medicine ·Vol. 186 ·No. 11 ·1997-12-01 ·Pages 1885-96

Ehrt S, Shiloh MU, Ruan J, Choi M, Gunzburg S, Nathan C, Xie Q, Riley LW

Abstract

Among the major antimicrobial products of macrophages are reactive intermediates of the oxidation of nitrogen (RNI) and the reduction of oxygen (ROI). Selection of recombinants in acidified nitrite led to the cloning of a novel gene, noxR1, from a pathogenic clinical isolate of Mycobacterium tuberculosis. Expression of noxR1 conferred upon Escherichia coli and Mycobacterium smegmatis enhanced ability to resist RNI and ROI, whether the bacteria were exposed to exogenous compounds in medium or to endogenous products in macrophages. These studies provide the first identification of an RNI resistance mechanism in mycobacteria, point to a new mechanism for resistance to ROI, and raise the possibility that inhibition of the noxR1 pathway might enhance the ability of macrophages to control tuberculosis.

MeSH Terms
Amino Acid Sequence Animals Antioxidants Bacterial Proteins/genetics,physiology Base Sequence Cloning, Molecular DNA, Bacterial/genetics Escherichia coli/genetics Genes, Bacterial Hydrogen Peroxide/metabolism Macrophages/metabolism,microbiology Mice Mice, Inbred C57BL Molecular Sequence Data Mycobacterium/genetics Mycobacterium tuberculosis/genetics Nitrites/metabolism Oxidation-Reduction Reactive Oxygen Species/metabolism Recombinant Fusion Proteins/metabolism Transfection Tuberculosis/immunology
Chemicals
Antioxidants Bacterial Proteins DNA, Bacterial Nitrites NoxR1 protein, Mycobacterium tuberculosis Reactive Oxygen Species Recombinant Fusion Proteins Hydrogen Peroxide
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Ehrt S
Division of International Medicine and Infectious Disease, Department of Medicine, Cornell University Medical College, New York 10021, USA.
Shiloh M U
Ruan J
Choi M
Gunzburg S
Nathan C
Xie Q
Riley L W
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.186.11.1885
Published
1997-12-01
Pages
1885-96
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2199150
Subset
IM
Grants
NIGMS NIH HHS · GM-07739 · United States
NHLBI NIH HHS · HL-51967 · United States
Databases
GENBANK
Y08323
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1084/jem.186.11.1885 PMC Full Text View journal details
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