Living on the edge: inhibition of host cell apoptosis by Mycobacterium tuberculosis

Tuberculosis is a human disease of global importance caused by infection with Mycobacterium tuberculosis. Thus, an estimated one-third of the world's population is latently infected; there are 2-3 million annual deaths and an increasing amount of multidrug-resistant and extensive drug-resistant tuberculosis cases. M. tuberculosis is a highly adapted human pathogen that has evolved to employ multiple strategies in its attempt to avoid an efficient host immune response. The induction of host cell death is an ancient immune defense strategy that is conserved throughout the animal and plant kingdoms. Here we review the current status of the research involving interaction of mycobacteria with host cells, regarding the induction of host cell death by apoptosis. We conclude that virulent strains of M. tuberculosis employ several strategies to avoid the induction of macrophage cell death, and success in this process is clearly important for bacterial virulence. The molecular mechanisms of host cell apoptosis inhibition are little understood, but the recent identification of anti-apoptosis genes in the genome of M. tuberculosis has provided the tools necessary to investigate the details of this host-pathogen interaction. The results of these future studies may prove useful for the development of new drug targets and/or vaccine candidates.