Mycobacterial genes essential for the pathogen's survival in the host

Mycobacterium tuberculosis (Mtb) has evolved within the human immune system as both host and reservoir. The study of genes required for its growth and persistence in vivo thus offers linked insights into its pathogenicity and host immunity. Studies of Mtb mutants have implicated metabolic adaptation (consisting of carbon, nitrogen, vitamin, and cofactor metabolism), intrabacterial pH homeostasis, and defense against reactive oxygen and reactive nitrogen species, as key determinants of its pathogenicity. However, the mechanisms of host immunity are complex and often combinatorial. Growing evidence has thus begun to reveal that the determinants of Mtb's pathogenicity may serve a broader and more complex array of functions than the isolated experimental settings in which they were initially found. Here, we review select examples, which exemplify this complexity, highlighting the distinct phases of Mtb's life cycle and the diverse microenvironments encountered therein.