Role of OxyS of Mycobacterium tuberculosis in oxidative stress: overexpression confers increased sensitivity to organic hydroperoxides

Mycobacterial genomics has uncovered a novel regulatory gene, oxyS, belongi ng to the LysR family. There is extensive similarity in the DNA-binding dom ain of OxyS with that of OxyR, the oxidative stress response protein of man y bacteria. Since the oxyR gene of Mycobacterium tuberculosis has been mult iply inactivated during evolution it was conceivable that some of its funct ions could be effected by OxyS. It is shown here that OxyS is produced at l ow levels and that there are at least three different oxyS alleles present in clinical isolates of M. tuberculosis that are susceptible or resistant t o isoniazid. Overproduction or depletion of OxyS did not affect susceptibil ity to isoniazid but increasing the concentration of the regulator lowered levels of the alkyl hydroperoxide reductase, AhpC, and rendered the tubercl e bacillus more susceptible to organic hydroperoxides. (C) 2001 Editions sc ientifiques et medicales Elsevier SAS.