{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T05:00:23Z","timestamp":1794373223723,"version":"4.9.0"},"reference-count":225,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Tuberculosis (TB), caused by\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (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.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1606311","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T01:27:56Z","timestamp":1750123676000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["The PE\/PPE family proteins of Mycobacterium tuberculosis: evolution, function, and prospects for tuberculosis control"],"prefix":"10.3389","volume":"16","author":[{"given":"Zhijing","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taibing","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinglan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ609","article-title":"Perspectives on advances in tuberculosis diagnostics, drugs, and vaccines","author":"Schito","year":"2015","journal-title":"Clin Infect 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