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

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 physiolog...

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Main Authors: Zhijing Zhang, Le Dong, Xin Li, Taibing Deng, Qinglan Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1606311/full
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author Zhijing Zhang
Zhijing Zhang
Le Dong
Xin Li
Taibing Deng
Qinglan Wang
author_facet Zhijing Zhang
Zhijing Zhang
Le Dong
Xin Li
Taibing Deng
Qinglan Wang
author_sort Zhijing Zhang
collection DOAJ
description 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.
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spelling doaj-art-e1630572f2384219ab04d2e7634b7f0a2025-08-20T02:07:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.16063111606311The PE/PPE family proteins of Mycobacterium tuberculosis: evolution, function, and prospects for tuberculosis controlZhijing Zhang0Zhijing Zhang1Le Dong2Xin Li3Taibing Deng4Qinglan Wang5Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaWest China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, ChinaCollege of Life Sciences, Sichuan University, Chengdu, Sichuan, ChinaSchool of Clinical Medicine, North Sichuan Medical College, Nanchong, Sichuan, ChinaSchool of Clinical Medicine, North Sichuan Medical College, Nanchong, Sichuan, ChinaInstitute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, ChinaTuberculosis (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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1606311/fullMycobacterium tuberculosisPE/PPEevolutionouter membraneporinvaccine
spellingShingle Zhijing Zhang
Zhijing Zhang
Le Dong
Xin Li
Taibing Deng
Qinglan Wang
The PE/PPE family proteins of Mycobacterium tuberculosis: evolution, function, and prospects for tuberculosis control
Frontiers in Immunology
Mycobacterium tuberculosis
PE/PPE
evolution
outer membrane
porin
vaccine
title The PE/PPE family proteins of Mycobacterium tuberculosis: evolution, function, and prospects for tuberculosis control
title_full The PE/PPE family proteins of Mycobacterium tuberculosis: evolution, function, and prospects for tuberculosis control
title_fullStr The PE/PPE family proteins of Mycobacterium tuberculosis: evolution, function, and prospects for tuberculosis control
title_full_unstemmed The PE/PPE family proteins of Mycobacterium tuberculosis: evolution, function, and prospects for tuberculosis control
title_short The PE/PPE family proteins of Mycobacterium tuberculosis: evolution, function, and prospects for tuberculosis control
title_sort pe ppe family proteins of mycobacterium tuberculosis evolution function and prospects for tuberculosis control
topic Mycobacterium tuberculosis
PE/PPE
evolution
outer membrane
porin
vaccine
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1606311/full
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