REVIEW article
Front. Microbiol.
Sec. Infectious Agents and Disease
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1695567
Beyond H37Rv: Mycobacterium tuberculosis pangenome structure and applications
Provisionally accepted
- 1División de Estudios de Posgrado, Universidad Michoacana de San Nicolas de Hidalgo Facultad de Ciencias Medicas y Biologicas Dr Ignacio Chavez, Morelia, Mexico
- 2Centro Multidisciplinario de Estudios en Biotecnología, Universidad Michoacana de San Nicolas de Hidalgo Facultad de Medicina Veterinaria y Zootecnia, Morelia, Mexico
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Mycobacterium tuberculosis (Mtb) is among the most successful bacterial pathogens, with multidrug-resistant strains posing significant challenges to global tuberculosis control. Traditional single-genome analyses, while essential for identifying strain-specific mutations, are limited in capturing the full spectrum of genetic diversity related to virulence, drug susceptibility, and transmission dynamics. Pangenomics examines the complete gene repertoire across all sequenced representatives of a species and addresses these limitations by enabling comprehensive, species-wide assessments of genetic variation. In this review, we summarize current knowledge of the Mtb pangenome, focusing on structural organization, methodological frameworks, and clinical applications. The Mtb pangenome exhibits a highly conserved genetic structure, with core genome estimates ranging from 1,166 to 3,767 genes, depending on the analytical thresholds and methodological approaches. Significant controversy regarding its classification as open or closed arises primarily from differences in computational pipelines (Roary, BPGA, Panaroo), core genome inclusion criteria (95-100% presence), and dataset composition rather than fundamental biological disagreement. Despite these methodological challenges, pangenomic applications have demonstrated transformative potential in molecular epidemiology, drug resistance prediction, and virulence profiling. This perspective underscores a shift toward diversity-inclusive approaches, with integration of machine learning and standardization of analytical protocols identified as key priorities for future tuberculosis research and therapeutic innovation.
Keywords: pangenome, Tuberculosis, core genome, pangenomic applications, MTBC
Received: 30 Aug 2025; Accepted: 24 Sep 2025.
Copyright: © 2025 Negrete-Paz, Vázquez-Marrufo and Vázquez-Garcidueñas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ma. Soledad Vázquez-Garcidueñas, soledad.vazquez@umich.mx
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