A novel antioxidant gene from Mycobacterium tuberculosis.
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.
Ehrt
S
S
Division of International Medicine and Infectious Disease, Department of Medicine, Cornell University Medical College, New York 10021, USA.
Shiloh
M U
MU
Ruan
J
J
Choi
M
M
Gunzburg
S
S
Nathan
C
C
Xie
Q
Q
Riley
L W
LW
D000595:Amino Acid Sequence; D000818:Animals; D000975:Antioxidants; D001426:Bacterial Proteins / Q000235:genetics* / Q000502:physiology; D001483:Base Sequence; D003001:Cloning, Molecular; D004269:DNA, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D005798:Genes, Bacterial; D006861:Hydrogen Peroxide / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009161:Mycobacterium / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D009573:Nitrites / Q000378:metabolism*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D014376:Tuberculosis / Q000276:immunology
D000975:Antioxidants; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D009573:Nitrites; C109372:NoxR1 protein, Mycobacterium tuberculosis; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D006861:Hydrogen Peroxide