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The PE/PPE family proteins of Mycobacterium tuberculosis: evolution, function, and prospects for tuberculosis control

Zhijing Zhang1,2, Le Dong3, Xin Li4

  • 1Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.

Frontiers in Immunology
|July 2, 2025
PubMed

Insights

Mycobacterium tuberculosis PE/PPE proteins are vital for bacterial survival and immune evasion. Understanding their evolution and function offers new avenues for developing effective tuberculosis vaccines and diagnostics.

Area of Science:

  • Microbiology
  • Immunology
  • Genomics

Background:

  • Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a major global health issue.
  • Drug resistance and poor vaccine efficacy complicate TB control efforts.
  • The PE/PPE protein family is unique to mycobacteria and crucial for Mtb's survival and interaction with hosts.

Purpose of the Study:

  • To review recent advancements in understanding the PE/PPE protein family in Mtb.
  • To explore the evolutionary, structural, and functional aspects of PE/PPE proteins.
  • To highlight the potential of PE/PPE proteins as targets for new TB diagnostics and vaccines.

Main Methods:

  • Literature review synthesizing current research on PE/PPE proteins and their associated Type VII Secretion Systems (T7SS).
  • Analysis of evolutionary patterns, structural diversity, and functional roles.
  • Examination of clinical progress and challenges in PE/PPE-based vaccine development.

Main Results:

  • PE/PPE proteins are key to Mtb's physiology, immune evasion, and pathogenesis.
  • These proteins co-evolve with T7SS, influencing nutrient acquisition and host immune responses.
  • Promising PE/PPE-based vaccine candidates (e.g., M72/AS01E, ID93/GLA-SE) show clinical potential.

Conclusions:

  • PE/PPE proteins represent a promising target family for next-generation TB interventions.
  • Overcoming challenges like epitope variability is essential for successful vaccine design.
  • Integrating diverse biological insights can accelerate the development of novel TB diagnostics and vaccines.
Keywords:
Mycobacterium tuberculosisPE/PPEevolutionouter membraneporinvaccine

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