Recent advances in antituberculosis drugs and therapeutics: from mechanistic breakthroughs to clinical translation

Tuberculosis (TB), caused by Mycobacterium tuberculosis, reclaimed its status as the deadliest single-pathogen infectious disease globally in 2023, accounting for 10.8 million new cases and 1.25 million deaths in 2023. 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.