Endosomal membrane traffic: convergence point targeted by Mycobacterium tuberculosis and HIV

Summary Inhibition of phagolysosome biogenesis in infected macrophages is a classical pathogenesis determinant of Mycobacterium tuberculosis . In this review we primarily cover the cellular mechanisms of M. tuberculosis phagosome maturation arrest. A detailed picture is beginning to emerge, involving regulators of membrane trafficking in mammalian cells and phagosomal interactions with endosomal organelles and the transGolgi network. We also present a hypothesis that overlaps may exist between the mycobacterial interference with the host cell membrane trafficking processes and the targeting of the late endosomal sorting machinery by HIV during viral budding in macrophages. We propose that interference with the endosomal sorting machinery contributes to the synergism between the two significant human diseases ‐ AIDS and tuberculosis. Mycobacterium tuberculosis macrophage parasitism Tuberculosis is a leading cause of death in the world, with 2‐3 million fatal cases annually. This is just the tip of an iceberg, because, by conservative estimates, close to a billion people are latently infected with M. tuberculosis . Even when completely asymptomatic, latently infected individuals run a 10% lifetime risk of eventually developing some form of active disease. The odds of progressing into overt tuberculosis increase to a staggering annual risk of 10% for individuals coinfected with HIV (World Health Organization tuberculosis fact sheet; http://www.who.int).