Mycobacterium tuberculosis is currently the etiologic agent that is responsible for the most deaths worldwide. Mycobacterium avium is the most common cause of systemic bacterial infection in American AIDS patients. Despite the public health importance of these diseases, the mechanisms of virulence remain unknown. We have adopted two strategies to identify mycobacterial virulence factors: 1) We are attempting to complement the virulence defect in an avirulent M. intracellulare strain with genes from a virulent M. avium strain. We have shown that some M. avium/M, intracellulare recombinants persist significantly better than the M. intracellulare host. Using the 2-D gel electrophoresis, we have identified differences in protein expression between the recombinant and host strains. We are currently attempting to establish the significance of these protein differences. These genetic complementation studies should allow us to identify M. avium genes which contribute to virulence. 2) The catalase-peroxidose (katG) protein has been shown to be a virulence factor in M. bovis BCG. We have also demonstrated that gene linked to katG is involved in virulence. We are currently evaluating the role of genes adjacent to katG in the virulence of M. tuberculosis.
