DISPARATE RESPONSES TO OXIDATIVE STRESS IN SAPROPHYTIC AND PATHOGENICMYCOBACTERIA

To persist in macrophages and in granulomatous caseous lesions, pathog enic mycobacteria must be equipped to withstand the action of toxic ox ygen metabolites, In Gram-negative bacteria, the OxyR protein is a cri tical component of the oxidative stress response. OxyR is both a senso r of reactive oxygen species and a transcriptional activator, inducing expression of detoxifying enzymes such as catalase/hydroperoxidase an d alkyl hydroperoxidase. We have characterized the responses of variou s mycobacteria to hydrogen peroxide both phenotypically and at the lev els of gene and protein expression. Only the saprophytic Mycobacterium smegmatis induced a protective oxidative stress response analogous to the OxyR response of Gram-negative bacteria, Under similar conditions , the pathogenic mycobacteria exhibited a limited, nonprotective respo nse, which in the case of Mycobacterium tuberculosis was restricted to induction of a single protein, KatG. We have also isolated DNA sequen ces homologous to oxyR and ahpC from M. tuberculosis and Mycobacterium avium. While the M. avium oxyR appears intact, the oxyR homologue of M. tuberculosis contains numerous deletions and frameshifts and is pro bably nonfunctional. Apparently the response of pathogenic mycobacteri a to oxidative stress differs significantly from the inducible OxyR re sponse of other bacteria.