Base by Base explores advances in genetics and genomics, with a focus on gene-disease associations, variant interpretation, protein structure, and insights from exome and genome sequencing. Each episode breaks down key studies and their clinical relevance—one base at a time.
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Base by Base explores advances in genetics and genomics, with a focus on gene-disease associations, variant interpretation, protein structure, and insights from exome and genome sequencing. Each episode breaks down key studies and their clinical relevance—one base at a time.
Powered by AI, Base by Base offers a new way to learn on the go. Special thanks to authors who publish under CC BY 4.0, making open-access science faster to share and easier to explore.
171: Virulence Hierarchies in the Tuberculosis Complex—What Makes Some Lineages Deadlier?
Base by Base
16 minutes 14 seconds
3 weeks ago
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/
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Base by Base
Base by Base explores advances in genetics and genomics, with a focus on gene-disease associations, variant interpretation, protein structure, and insights from exome and genome sequencing. Each episode breaks down key studies and their clinical relevance—one base at a time.
Powered by AI, Base by Base offers a new way to learn on the go. Special thanks to authors who publish under CC BY 4.0, making open-access science faster to share and easier to explore.
