J. Exp. Med., Volume 186, Number 11, December 1, 1997 1885-1896

A Novel Antioxidant Gene from Mycobacterium tuberculosis

By Sabine Ehrt,^* Michael U. Shiloh, Jia Ruan, Michael Choi,^* Stuart Gunzburg,^* Carl Nathan, Qiao-wen Xie, and Lee W. Riley^*

From the ^* Division of International Medicine and Infectious Disease and  Division of Hematology-Oncology, Department of Medicine, Cornell University Medical College, New York 10021

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.

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