Anti-apoptotic strategies of M. tuberculosis

Mycobacterium tuberculosis, one of most successful pathogens of mankind, infects one-third of the global population claiming nearly two million lives every year. The pathogen exhibits extraordinary capacities to evade host responses to survive within the host. One of the hallmarks is its ability to inhibit apoptosis to promote intracellular survival. Understanding the mechanism of inhibition of infection-induced apoptosis and the signaling pathway involved may help reveal salient components of host defense. The study described in this thesis dissects the ability of this deadly pathogen in hijacking the host responses to infection and how this can be exploited for design of better vaccines against Tuberculosis. The crux of the thesis is the identification of a new gene of M. tuberculosis, nlaA, and its gene product, a secreted protein. The thesis further describes the design of a novel attenuated vaccine, by knocking-out the gene from M. tuberculosis. The vaccine candidate thus developed is attenuated, inflicts less pathological changes in the organs of infected mice and protects against experimental tuberculosis.