Tuberculosis remains a serious threat to global public health. As one of the most successful pathogens, Mycobacterium tuberculosis is an adept in evasion the host immune response. M. tuberculosis PE_PGRS family has been widely proposed as molecular mantra to deflect host immunity. The feature of this family is the conserved N-terminal and variable C-terminal. PE_PGRS proteins, with functions largely unknown, are only found among mycobacteria and located in the mycobacterial cell wall and cell membrane. Most PE_PGRS proteins have antigenicity. Polymorphic PGRS domain might play a role in neutralize immune response. Several members of PE_PGRS family have been heterologously expressed for further function characterization. PE_PGRS gene expressing stage-specifically, especially during M. tuberculosis persistence, is promising intervention target to prevent reactivation. The origin, physiological role and spatiotemporal regulation feature of this family remain elusive. The understanding of these questions will shed light on the pathogenesis of M. tuberculosis and facilitate the discovery of new effective antibacterial intervention.
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