Bovine and human TB: probing the genetic, molecular and structural basis of lipid-mediated pathogenesis mechanisms.

Tuberculosis is one of the greatest causes of death due to an infectious disease worldwide (joint with HIV). It is caused by members of the Mycobacterium tuberculosis (MTB) complex, which demonstrate 99.9% similarity at a nucleotide level (Boddinghaus, B. et al., 1990) yet differ greatly in their host trophism and pathogenicity. This project will focus mainly on the evolution of members of the MTB complex. One approach will involve delineating differences between two members, Mycobacterium tuberculosis (M. tuberculosis) and Mycobacterium bovis (M. bovis) through the generation of knockout recombinant strains that represent intermediates in the evolution of these pathogens; these strains will be employed in infection studies. A second approach involves the utilisation of differing cell lines in similar infection studies, due to the tissue trophism observed during mycobacterial infection. Finally, a third approach will involve delineating the fundamental processes that drive pathogenicity, to determine the differences between non-pathogenic environmental pathogens from pathogenic members of the MTB complex.