Ins and outs of Mycobacterium tuberculosis PPE family in pathogenesis and implications for novel measures against tuberculosis

Mycobacterium tuberculosis is the most successful pathogen with multiple mechanisms to subvert host immune response, resulting in insidious disease. A unique Mycobacterium antigen family termed PPE (Pro-Pro-Glu) has long been widely speculated as "molecular mantra" to escape host immunity. Members of this family are characterized by a conserved N terminal and a variable C terminal. This family associated closely with ESAT-6(ESX) secretion system and largely located in cell wall or cell membrane. The expression of PPE protein is temporally regulated, and highly expressed during M. tuberculosis persistence. Importantly, the distribution of PPE family is so far limited to Mycobacterium genus, prevalent among pathogenic Mycobacterium species. It is tempting to explore this family due to its potential in the latency and reactivation of M. tuberculosis. The evolution, structure, and functions of most PPE proteins remain elusive. The understanding of these questions will deepen our appreciation of the pathogenesis of M. tuberculosis and accelerate novel anti-TB measures discovery.