A NOVEL ANTIOXIDANT GENE FROM MYCOBACTERIUM-TUBERCULOSIS

Among the major antimicrobial products of macrophages are reactive int ermediates of the oxidation of nitrogen (RNI) and the reduction of oxy gen (ROI). Selection of recombinants in acidified nitrite led to the c loning of a novel gene, MoxR1, from a pathogenic clinical isolate of M ycobacterium tuberculosis. Expression of noxR1 conferred upon Escheric hia call and Mycobacterium smegmatis enhanced ability to resist RNI an d ROI, whether the bacteria were exposed to exogenous compounds in med ium or to endogenous products in macrophages. These studies provide th e first identification of an RNI resistance mechanism in mycobacteria, point to a new mechanism for resistance to ROI, and raise the possibi lity that inhibition of the noxR1 pathway might enhance the ability of macrophages to control tuberculosis.