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The escalating crisis of drug-resistant TB, suboptimal BCG vaccine efficacy in adults, and persistent treatment gaps for vulnerable populations collectively drive an urgent shift toward mechanism-driven, precision-oriented therapeutic strategies.This review presents a critically integrated appraisal of anti-TB research advances spanning 2020 to 2025, drawing on structural biology, multi-omics, and real-world clinical evidence. It distinguishes itself from conventional descriptive literature compilations through systematic cross-population efficacy comparisons, in-depth dissection of translational bottlenecks, and explicit maturity stratification of emerging biotherapies. We synthesize progress across six interconnected domains: mechanistic insights into drug targets and spatiotemporal resistance evolution, novel short-course therapeutic regimens, precision medicine strategies, host-directed therapies, targeted delivery systems for extrapulmonary TB, and next-generation vaccine development. Three transformative breakthroughs are particularly highlighted: structural biology-guided rational drug design, spatial immune profiling of tuberculous granulomas, and AI-assisted diagnostic pipelines.We conclude by delineating priority research directions aligned with the WHO End TB Strategy, providing a translational roadmap to advance global TB elimination efforts. This rigorous, multi-dimensional synthesis offers an authoritative reference for advancing basic and translational anti-TB research and informing global public health strategy.<\/jats:p>","DOI":"10.1186\/s43556-026-00610-5","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:01:10Z","timestamp":1791662470000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Recent advances in antituberculosis drugs and therapeutics: from mechanistic breakthroughs to clinical translation"],"prefix":"10.1186","volume":"7","author":[{"given":"Zhixiang","family":"Pan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hegui","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongri","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5322-9667","authenticated-orcid":false,"given":"Shuang","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,10]]},"reference":[{"key":"610_CR1","doi-asserted-by":"publisher","unstructured":"Clark RA, Weerasuriya CK, Portnoy A, Mukandavire C, Quaife M, Bakker R, et al. 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