171: Virulence Hierarchies in the Tuberculosis Complex—What Makes Some Lineages Deadlier?

️ Episode 171: Virulence Hierarchies in the Tuberculosis Complex—What Makes Some Lineages Deadlier? In this episode of PaperCast Base by Base, we explore a new PNAS study that directly compares the virulence of Mycobacterium tuberculosis, M. bovis, and M. orygis across natural and laboratory hosts to uncover why animal-adapted lineages can be so devastating. Study Highlights:The authors performed side-by-side infections in Holstein calves and C57BL/6 mice, showing that M. bovis and M. orygis consistently caused more severe disease, faster mortality, and higher bacterial burdens than M. tuberculosis. Comparative proteomics identified ESAT‑6/CFP‑10 and the SigK‑regulated antigen MPT70 as prominent secreted factors in animal-adapted lineages, and gene deletions reversed the lethal phenotype for M. bovis but not for M. orygis. Disease outcomes depended on infection route and immune history, with oral priming, BCG vaccination, and a multisubunit vaccine (H107e) markedly prolonging survival after aerosol challenge. Together, the data establish a clear virulence hierarchy within the MTBC and point to lineage‑informed antigen choices for future vaccines and control strategies. Conclusion:Animal-adapted MTBC members can be hypervirulent compared with M. tuberculosis, and their distinct antigenic profiles and route‑dependent biology offer actionable clues for next‑generation zoonotic and human TB vaccines. Reference:Danchuk SN, Duffy SC, Sullivan J, Rufai SB, McIntosh FA, Lupien A, Harrison LB, et al. Virulence hierarchies within the Mycobacterium tuberculosis complex. Proceedings of the National Academy of Sciences. 2025;122(42):e2507104122. https://doi.org/10.1073/pnas.2507104122 License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:If you'd like to support Base by Base, you can make a one-time or monthly donation here: https://basebybase.castos.com/ Chapters (00:00:00) - Virulence hierarchies within the Mycobacterium Tu(00:03:17) - Fighting mbovin in the calf(00:06:05) - M. Bovis vs Amorgis TB pathogenesis(00:09:58) - MTBC virulence and the big mystery(00:11:52) - Immunity studies of human TB(00:13:48) - Animal-adapted TB

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