Zhang Zhijing, Dong Le, Li Xin, Deng Taibing, Wang Qinglan
Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, China.
Front Immunol. 2025 Jun 17;16:1606311. doi: 10.3389/fimmu.2025.1606311. eCollection 2025.
Tuberculosis (TB), caused by (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.
由结核分枝杆菌（Mtb）引起的结核病（TB）仍然是全球主要的健康威胁，耐药性和疫苗效力不足加剧了这一威胁。PE/PPE蛋白家族是分枝杆菌特有的，约占Mtb基因组的10%，在细菌生理学、免疫逃避和宿主-病原体相互作用中发挥关键作用。本综述综合了在理解PE/PPE蛋白的进化扩张、结构多样性和功能多样性方面的进展，强调了它们与VII型分泌系统（T7SS）的共同进化。我们重点介绍了它们在营养获取、免疫调节和发病机制中的作用，以及它们作为诊断和疫苗靶点的潜力。基于PE/PPE的疫苗，如M72/AS01E和ID93/GLA-SE的临床进展，凸显了它们在抗击结核病方面的前景，而表位变异性和功能冗余方面的挑战则需要创新策略。通过整合进化、结构和免疫学见解，本综述为利用PE/PPE生物学开发下一代结核病干预措施提供了路线图。
