EXPRESSION OF KATG IN MYCOBACTERIUM-TUBERCULOSIS IS ASSOCIATED WITH ITS GROWTH AND PERSISTENCE IN MICE AND GUINEA-PIGS

The molecular mechanisms associated with the pathogenesis of tuberculo sis are not well understood. The present study evaluated the role of c atalase-peroxidase as a potential virulence factor for Mycobacterium t uberculosis. Growth and persistence of M. tuberculosis H37Rv in intrav enously infected BALB/c mice were compared with katG-deleted, isoniazi d-resistant M. tuberculosis H37RvINH(R). Transformation of M. tubercul osis H37Rv (TBkatG) or Mycobacterium intracellulare (MACkatG) genes in to M. tuberculosis H37RvINH(R) restored its catalase-peroxidase activi ties and the ability of the recombinants to persist in spleens of mice and guinea pigs. Transformation with the TBkatG gene with the codon 4 63 R-->L mutation also restored catalase-peroxidase activity and enhan ced persistence. However, transformants with the codon 275 T-->P mutan t expressed low levels of enzymatic activity and failed to persist in guinea pig spleen, although they did survive in mouse tissues. These r esults indicate that KatG contributes to the ability of M. tuberculosi s to grow and survive within the infected host tissues.