REVIEW article
Front. Immunol.
Sec. Microbial Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1606311
This article is part of the Research TopicDeciphering Host-Pathogen Interactions in Tuberculosis: Implications for Diagnostics and TherapeuticsView all 6 articles
The PE/PPE Family Proteins of Mycobacterium tuberculosis: Evolution, Function, and Prospects for Tuberculosis Control
Provisionally accepted
- 1Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Chengdu, Sichuan Province, China
- 2West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan Province, China
- 3College of Life Science, Sichuan University, Chengdu, Sichuan Province, China
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Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a leading global health threat, exacerbated by drug resistance and inadequate vaccine efficacy. The PE/PPE protein family, unique to mycobacteria, constitutes ~10% of the Mtb genome and plays critical roles in bacterial physiology, immune evasion, and host-pathogen interactions. This review synthesizes advances in understanding the evolutionary expansion, structural diversity, and functional versatility of PE/PPE proteins, emphasizing their co-evolution with type VII secretion systems (T7SS). We highlight their roles in nutrient acquisition, immune modulation, and pathogenesis, alongside their potential as diagnostic and vaccine targets. Clinical progress in PE/PPE-based vaccines, such as M72/AS01E and ID93/GLA-SE, underscores their promise in combating TB, while challenges in epitope variability and functional redundancy demand innovative strategies. By integrating evolutionary, structural, and immunological insights, this review provides a roadmap for leveraging PE/PPE biology to develop next-generation TB interventions.
Keywords: Mycobacterium tuberculosis, PE/PPE, evolution, outer membrane, porin, Vaccine
Received: 05 Apr 2025; Accepted: 30 May 2025.
Copyright: © 2025 Wang, Zhang and Dong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Qinglan Wang, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Chengdu, 610041, Sichuan Province, China
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