World Health Organization. Global tuberculosis report 2024 (WHO, 2024).
Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 399, 629–655 (2022).
Farhat, M. et al. Drug-resistant tuberculosis: a persistent global health concern. Nat. Rev. Microbiol. 22, 617–635 (2024).
Gagneux, S. Ecology and evolution of Mycobacterium tuberculosis. Nat. Rev. Microbiol. 16, 202–213 (2018).
World Health Organization. Roadmap for zoonotic tuberculosis (WHO, 2017).
Orgeur, M., Sous, C., Madacki, J. & Brosch, R. Evolution and emergence of Mycobacterium tuberculosis. FEMS Microbiol. Rev. 48, fuae006 (2024).
Pepperell, C. S. Evolution of tuberculosis pathogenesis. Annu. Rev. Microbiol. 76, 661–680 (2022).
Chiner-Oms, Á. et al. Genomic determinants of speciation and spread of the Mycobacterium tuberculosis complex. Sci. Adv. 5, eaaw3307 (2019).
Ceres, K. M., Stanhope, M. J. & Gröhn, Y. T. A critical evaluation of pangenomics, with reference to its utility in outbreak investigation. Microb. Genom. 8, mgen000839 (2022).
Stritt, C. & Gagneux, S. How do monomorphic bacteria evolve? The Mycobacterium tuberculosis complex and the awkward population genetics of extreme clonality. Peer Community J. 3, e92 (2023).
Meehan, C. J. et al. Whole genome sequencing of Mycobacterium tuberculosis: current standards and open issues. Nat. Rev. Microbiol. 17, 533–545 (2019).
Brites, D. et al. A new phylogenetic framework for the animal-adapted Mycobacterium tuberculosis complex. Front. Microbiol. 9, 2820 (2018).
Malone, K. M. & Gordon, S. V. Mycobacterium tuberculosis complex members adapted to wild and domestic animals. Adv. Exp. Med. Biol. 1019, 135–154 (2017).
Coscolla, M. et al. Novel Mycobacterium tuberculosis complex isolate from a wild chimpanzee. Emerg. Infect. Dis. 19, 969–976 (2013).
Coscolla, M. et al. Phylogenomics of Mycobacterium africanum reveals a new lineage and a complex evolutionary history. Microb. Genom. 7, 000477 (2021).
Guyeux, C. et al. Newly identified Mycobacterium africanum lineage 10, central Africa. Emerg. Infect. Dis. 30, 560–563 (2024).
Bos, K. I. et al. Pre-Columbian mycobacterial genomes reveal seals as a source of New World human tuberculosis. Nature 514, 494–497 (2014).
Vågene, Å. J. et al. Geographically dispersed zoonotic tuberculosis in pre-contact South American human populations. Nat. Commun. 13, 1195 (2022).
Orgeur, M. et al. Pathogenomic analyses of Mycobacterium microti, an ESX-1-deleted member of the Mycobacterium tuberculosis complex causing disease in various hosts. Microb. Genom. 7, 000505 (2021).
Wells, A. Q. Tuberculosis in wild voles. Lancet 229, 1221 (1937).
Ghielmetti, G. et al. Mycobacterium microti infections in free-ranging red deer (Cervus elaphus). Emerg. Infect. Dis. 27, 2025–2032 (2021).
Brynildsrud, O. B. et al. Global expansion of Mycobacterium tuberculosis lineage 4 shaped by colonial migration and local adaptation. Sci. Adv. 4, eaat5869 (2018).
Zwyer, M. et al. A new nomenclature for the livestock-associated Mycobacterium tuberculosis complex based on phylogenomics. Open Res. Eur. 1, 100 (2021).
Loiseau, C. et al. An African origin for Mycobacterium bovis. Evol. Med. Public Health 2020, 49–59 (2020).
Pereira, A. C., Pinto, D. & Cunha, M. V. First time whole genome sequencing of Mycobacterium bovis from the environment supports transmission at the animal–environment interface. J. Hazard. Mater. 472, 134473 (2024).
Allen, A. R., Ford, T. & Skuce, R. A. Does Mycobacterium tuberculosis var. bovis survival in the environment confound bovine tuberculosis control and eradication? A literature review. Vet. Med. Int. 2021, 8812898 (2021).
Duffy, S. C., Marais, B., Kapur, V. & Behr, M. A. Zoonotic tuberculosis in the 21st century. Lancet Infect. Dis. 24, 339–341 (2024).
Refaya, A. K. et al. Whole-genome sequencing of a Mycobacterium orygis strain isolated from cattle in Chennai, India. Microbiol. Resour. Announc. 8, e01080–e0119 (2019).
Jawahar, A., Dhinakar Raj, G., Pazhanivel, N. & Karthik, K. Gross and histopathological features of tuberculosis in cattle, buffalo and spotted deer (Axis axis) caused by Mycobacterium orygis. J. Comp. Pathol. 208, 15–19 (2024).
Loiseau, C. et al. The relative transmission fitness of multidrug-resistant Mycobacterium tuberculosis in a drug resistance hotspot. Nat. Commun. 14, 1988 (2023).
Chitwood, M. H. et al. The recent rapid expansion of multidrug resistant Ural lineage Mycobacterium tuberculosis in Moldova. Nat. Commun. 15, 2962 (2024).
Goig, G. A. et al. Effect of compensatory evolution in the emergence and transmission of rifampicin-resistant Mycobacterium tuberculosis in Cape Town, South Africa: a genomic epidemiology study. Lancet Microbe 4, e506–e515 (2023).
Brown, T. S. et al. Pre-detection history of extensively drug-resistant tuberculosis in KwaZulu-Natal, South Africa. Proc. Natl Acad. Sci. USA 116, 23284–23291 (2019).
de Jong, B. C., Antonio, M. & Gagneux, S. Mycobacterium africanum — review of an important cause of human tuberculosis in West Africa. PLoS Negl. Trop. Dis. 4, e744 (2010).
Firdessa, R. et al. Mycobacterial lineages causing pulmonary and extrapulmonary tuberculosis, Ethiopia. Emerg. Infect. Dis. 19, 460–463 (2013).
Ngabonziza, J. C. S. et al. A sister lineage of the Mycobacterium tuberculosis complex discovered in the African Great Lakes region. Nat. Commun. 11, 2917 (2020).
Comas, I. et al. Population genomics of Mycobacterium tuberculosis in Ethiopia contradicts the virgin soil hypothesis for human tuberculosis in sub-Saharan Africa. Curr. Biol. 25, 3260–3266 (2015).
Supply, P. et al. Genomic analysis of smooth tubercle bacilli provides insights into ancestry and pathoadaptation of Mycobacterium tuberculosis. Nat. Genet. 45, 172–179 (2013).
Yenew, B. et al. A smooth tubercle bacillus from Ethiopia phylogenetically close to the Mycobacterium tuberculosis complex. Nat. Commun. 14, 7519 (2023).
O’Neill, M. B. et al. Lineage specific histories of Mycobacterium tuberculosis dispersal in Africa and Eurasia. Mol. Ecol. 28, 3241–3256 (2019).
Rutaihwa, L. K. et al. Multiple introductions of Mycobacterium tuberculosis lineage 2–Beijing into Africa over centuries. Front. Ecol. Evol. 7, 112 (2019).
Menardo, F. et al. Local adaptation in populations of Mycobacterium tuberculosis endemic to the Indian Ocean rim. F1000Res. 10, 60 (2021).
Shuaib, Y. A. et al. Origin and global expansion of Mycobacterium tuberculosis complex lineage 3. Genes 13, 990 (2022).
Zwyer, M. et al. Back-to-Africa introductions of Mycobacterium tuberculosis as the main cause of tuberculosis in Dar es Salaam, Tanzania. PLoS Pathog. 19, e1010893 (2023).
López, M. G. et al. Tuberculosis in Liberia: high multidrug-resistance burden, transmission and diversity modelled by multiple importation events. Microb. Genom. 6, e000325 (2020).
Stucki, D. et al. Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages. Nat. Genet. 48, 1535–1543 (2016).
Hershberg, R. et al. High functional diversity in Mycobacterium tuberculosis driven by genetic drift and human demography. PLoS Biol. 6, e311 (2008).
Kay, G. L. et al. Eighteenth-century genomes show that mixed infections were common at time of peak tuberculosis in Europe. Nat. Commun. 6, 6717 (2015).
Sabin, S. et al. A seventeenth-century Mycobacterium tuberculosis genome supports a Neolithic emergence of the Mycobacterium tuberculosis complex. Genome Biol. 21, 201 (2020).
Comas, I. et al. Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans. Nat. Genet. 45, 1176–1182 (2013).
Silcocks, M. & Dunstan, S. J. Parallel signatures of Mycobacterium tuberculosis and human Y-chromosome phylogeography support the Two Layer model of East Asian population history. Commun. Biol 6, 1037 (2023).
Menardo, F., Duchêne, S., Brites, D. & Gagneux, S. The molecular clock of Mycobacterium tuberculosis. PLoS Pathog. 15, e1008067 (2019).
Menardo, F., Gagneux, S. & Freund, F. Multiple merger genealogies in outbreaks of Mycobacterium tuberculosis. Mol. Biol. Evol. 38, 290–306 (2021).
Duchêne, S. et al. Genome-scale rates of evolutionary change in bacteria. Microb. Genom. 2, e000094 (2016).
Wiens, K. E. et al. Global variation in bacterial strains that cause tuberculosis disease: a systematic review and meta-analysis. BMC Med. 16, 196 (2018).
World Health Organization. Global tuberculosis report 2022 (WHO, 2022).
Netikul, T., Palittapongarnpim, P., Thawornwattana, Y. & Plitphonganphim, S. Estimation of the global burden of Mycobacterium tuberculosis lineage 1. Infect. Genet. Evol. 91, 104802 (2021).
Mitchison, D. A., Selkon, J. B. & Lloyd, J. Virulence in the guinea-pig, susceptibility to hydrogen peroxide, and catalase activity of isoniazid-sensitive tubercle bacilli from south Indian and British patients. J. Pathol. Bacteriol. 86, 377–386 (1963).
Bottai, D. et al. TbD1 deletion as a driver of the evolutionary success of modern epidemic Mycobacterium tuberculosis lineages. Nat. Commun. 11, 684 (2020).
Brosch, R. et al. A new evolutionary scenario for the Mycobacterium tuberculosis complex. Proc. Natl Acad. Sci. USA 99, 3684–3689 (2002).
Bateson, A. et al. Ancient and recent differences in the intrinsic susceptibility of Mycobacterium tuberculosis complex to pretomanid. J. Antimicrob. Chemother. 77, 1685–1693 (2022).
Rupasinghe, P. et al. Refined understanding of the impact of the Mycobacterium tuberculosis complex diversity on the intrinsic susceptibility to pretomanid. Microbiol. Spectr. 12, e0007024 (2024).
Stanley, S. et al. Identification of bacterial determinants of tuberculosis infection and treatment outcomes: a phenogenomic analysis of clinical strains. Lancet Microbe 5, e570–e580 (2024).
Van Rie, A. et al. Balancing access to BPaLM regimens and risk of resistance. Lancet Infect. Dis. 22, 1411–1412 (2022).
Borrell, S. et al. Reference set of Mycobacterium tuberculosis clinical strains: a tool for research and product development. PLoS ONE 14, e0214088 (2019).
Du, D. H. et al. The effect of M. tuberculosis lineage on clinical phenotype. PLoS Glob. Public Health 3, e0001788 (2023).
An ancestral mycobacterial effector promotes dissemination of infection. Cell 185, 4507–4525.e18 (2022).
Holt, K. E. et al. Frequent transmission of the Mycobacterium tuberculosis Beijing lineage and positive selection for the EsxW Beijing variant in Vietnam. Nat. Genet. 50, 849–856 (2018).
Freschi, L. et al. Population structure, biogeography and transmissibility of Mycobacterium tuberculosis. Nat. Commun. 12, 6099 (2021).
Gröschel, M. I. et al. Differential rates of Mycobacterium tuberculosis transmission associate with host–pathogen sympatry. Nat. Microbiol. 9, 2113–2127 (2024).
Coussens, A. K. et al. Classification of early tuberculosis states to guide research for improved care and prevention: an international Delphi consensus exercise. Lancet Respir. Med. 12, 484–498 (2024).
Long, R. et al. The association between phylogenetic lineage and the subclinical phenotype of pulmonary tuberculosis: a retrospective 2-cohort study. J. Infect. 88, 123–131 (2024).
Brites, D. & Gagneux, S. Co-evolution of Mycobacterium tuberculosis and Homo sapiens. Immunol. Rev. 264, 6–24 (2015).
Hirsh, A. E., Tsolaki, A. G., DeRiemer, K., Feldman, M. W. & Small, P. M. Stable association between strains of Mycobacterium tuberculosis and their human host populations. Proc. Natl Acad. Sci. USA 101, 4871–4876 (2004).
Baker, L., Brown, T., Maiden, M. C. & Drobniewski, F. Silent nucleotide polymorphisms and a phylogeny for Mycobacterium tuberculosis. Emerg. Infect. Dis. 10, 1568–1577 (2004).
Gagneux, S. et al. Variable host–pathogen compatibility in Mycobacterium tuberculosis. Proc. Natl Acad. Sci. USA 103, 2869–2873 (2006).
Reed, M. B. et al. Major Mycobacterium tuberculosis lineages associate with patient country of origin. J. Clin. Microbiol. 47, 1119–1128 (2009).
Fenner, L. et al. HIV infection disrupts the sympatric host–pathogen relationship in human tuberculosis. PLoS Genet. 9, e1003318 (2013).
Liu, Q. et al. Local adaptation of Mycobacterium tuberculosis on the Tibetan Plateau. Proc. Natl Acad. Sci. USA 118, e2017831118 (2021).
Luo, Y. et al. Paired analysis of host and pathogen genomes identifies determinants of human tuberculosis. Nat. Commun. 15, 10393 (2024).
Xu, Z. M. et al. Genome-to-genome analysis reveals associations between human and mycobacterial genetic variation in tuberculosis patients from Tanzania. Preprint at medRxiv https://doi.org/10.1101/2023.05.11.23289848 (2023).
Comas, I. et al. Human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved. Nat. Genet. 42, 498–503 (2010).
Coscolla, M. et al. M. tuberculosis T cell epitope analysis reveals paucity of antigenic variation and identifies rare variable TB antigens. Cell Host Microbe 18, 538–548 (2015).
McHenry, M. L. et al. Interaction between host genes and Mycobacterium tuberculosis lineage can affect tuberculosis severity: evidence for coevolution? PLoS Genet. 16, e1008728 (2020).
Woolhouse, M. E. J., Webster, J. P., Domingo, E., Charlesworth, B. & Levin, B. R. Biological and biomedical implications of the co-evolution of pathogens and their hosts. Nat. Genet. 32, 569–577 (2002).
Osei-Wusu, S. et al. Macrophage susceptibility to infection by Ghanaian Mycobacterium tuberculosis complex lineages 4 and 5 varies with self-reported ethnicity. Front. Cell. Infect. Microbiol. 13, 1163993 (2023).
Asante-Poku, A. et al. Mycobacterium africanum is associated with patient ethnicity in Ghana. PLoS Negl. Trop. Dis. 9, e3370 (2015).
Asante-Poku, A. et al. Molecular epidemiology of Mycobacterium africanum in Ghana. BMC Infect. Dis. 16, 385 (2016).
Hiza, H. et al. Bacterial diversity dominates variable macrophage responses of tuberculosis patients in Tanzania. Sci. Rep. 14, 9287 (2024).
Borrell, S. & Gagneux, S. Infectiousness, reproductive fitness and evolution of drug-resistant Mycobacterium tuberculosis. Int. J. Tuberc. Lung Dis. 13, 1456–1466 (2009).
Torres Ortiz, A. et al. Genomic signatures of pre-resistance in Mycobacterium tuberculosis. Nat. Commun. 12, 7312 (2021).
Ebrahimi-Rad, M. et al. Mutations in putative mutator genes of Mycobacterium tuberculosis strains of the W-Beijing family. Emerg. Infect. Dis. 9, 838–845 (2003).
Werngren, J. & Hoffner, S. E. Drug-susceptible Mycobacterium tuberculosis Beijing genotype does not develop mutation-conferred resistance to rifampin at an elevated rate. J. Clin. Microbiol. 41, 1520–1524 (2003).
Ford, C. B. et al. Mycobacterium tuberculosis mutation rate estimates from different lineages predict substantial differences in the emergence of drug-resistant tuberculosis. Nat. Genet. 45, 784–790 (2013).
Carey, A. F. et al. TnSeq of Mycobacterium tuberculosis clinical isolates reveals strain-specific antibiotic liabilities. PLoS Pathog. 14, e1006939 (2018).
Castro, R. A. D. et al. The genetic background modulates the evolution of fluoroquinolone-resistance in Mycobacterium tuberculosis. Mol. Biol. Evol. 37, 195–207 (2020).
Gagneux, S. et al. The competitive cost of antibiotic resistance in Mycobacterium tuberculosis. Science 312, 1944–1946 (2006).
Comas, I. et al. Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes. Nat. Genet. 44, 106–110 (2011).
Casali, N. et al. Evolution and transmission of drug-resistant tuberculosis in a Russian population. Nat. Genet. 46, 279–286 (2014).
Merker, M. et al. Compensatory evolution drives multidrug-resistant tuberculosis in Central Asia. eLife 7, e38200 (2018).
Gygli, S. M. et al. Prisons as ecological drivers of fitness-compensated multidrug-resistant Mycobacterium tuberculosis. Nat. Med. 27, 1171–1177 (2021).
Merker, M. et al. Transcontinental spread and evolution of Mycobacterium tuberculosis W148 European/Russian clade toward extensively drug resistant tuberculosis. Nat. Commun. 13, 5105 (2022).
Ngabonziza, J. C. S. et al. Multidrug-resistant tuberculosis control in Rwanda overcomes a successful clone that causes most disease over a quarter century. J. Clin. Tuberc. Other Mycobact. Dis. 27, 100299 (2022).
Eldholm, V. et al. Four decades of transmission of a multidrug-resistant Mycobacterium tuberculosis outbreak strain. Nat. Commun. 6, 7119 (2015).
Dixit, A. et al. Modern lineages of Mycobacterium tuberculosis were recently introduced in western India and demonstrate increased transmissibility. Open Forum Infect. Dis. 8, 783–784 (2021).
Shanmugam, S. K. et al. Mycobacterium tuberculosis lineages associated with mutations and drug resistance in isolates from India. Microbiol. Spectr. 10, e0159421 (2022).
Dreyer, V. et al. High fluoroquinolone resistance proportions among multidrug-resistant tuberculosis driven by dominant L2 Mycobacterium tuberculosis clones in the Mumbai metropolitan region. Genome Med. 14, 95 (2022).
Castro, R. A. D., Borrell, S. & Gagneux, S. The within-host evolution of antimicrobial resistance in Mycobacterium tuberculosis. FEMS Microbiol. Rev. 45, fuaa071 (2021).
Morales-Arce, A. Y., Sabin, S. J., Stone, A. C. & Jensen, J. D. The population genomics of within-host Mycobacterium tuberculosis. Heredity 126, 1–9 (2021).
Trauner, A. et al. The within-host population dynamics of Mycobacterium tuberculosis vary with treatment efficacy. Genome Biol. 18, 71 (2017).
Nimmo, C. et al. Dynamics of within-host Mycobacterium tuberculosis diversity and heteroresistance during treatment. EBioMedicine 55, 102747 (2020).
Vargas, R. et al. In-host population dynamics of Mycobacterium tuberculosis complex during active disease. eLife 10, e61805 (2021).
Liu, Q. et al. Mycobacterium tuberculosis clinical isolates carry mutational signatures of host immune environments. Sci. Adv. 6, eaba4901 (2020).
Smith, T. M. et al. Rapid adaptation of a complex trait during experimental evolution of Mycobacterium tuberculosis. eLife 11, e78454 (2022).
Lieberman, T. D. et al. Genomic diversity in autopsy samples reveals within-host dissemination of HIV-associated Mycobacterium tuberculosis. Nat. Med. 22, 1470–1474 (2016).
Liu, Q. et al. Within patient microevolution of Mycobacterium tuberculosis correlates with heterogeneous responses to treatment. Sci. Rep. 5, 17507 (2015).
Moreno-Molina, M. et al. Genomic analyses of Mycobacterium tuberculosis from human lung resections reveal a high frequency of polyclonal infections. Nat. Commun. 12, 2716 (2021).
Martin, C. J. et al. Digitally barcoding Mycobacterium tuberculosis reveals in vivo infection dynamics in the macaque model of tuberculosis. mBio 8, e00312–e00317 (2017).
Levin, B. R. & Bull, J. J. Short-sighted evolution and the virulence of pathogenic microorganisms. Trends Microbiol. 2, 76–81 (1994).
Cadena, A. M. et al. Concurrent infection with Mycobacterium tuberculosis confers robust protection against secondary infection in macaques. PLoS Pathog. 14, e1007305 (2018).
Nemeth, J. et al. Contained Mycobacterium tuberculosis infection induces concomitant and heterologous protection. PLoS Pathog. 16, e1008655 (2020).
Ganchua, S. K. et al. Antibiotic treatment modestly reduces protection against Mycobacterium tuberculosis reinfection in macaques. Infect. Immun. 92, e0053523 (2024).
Andrews, J. R. et al. Risk of progression to active tuberculosis following reinfection with Mycobacterium tuberculosis. Clin. Infect. Dis. 54, 784–791 (2012).
Guerra-Assunção, J. A. et al. Recurrence due to relapse or reinfection with Mycobacterium tuberculosis: a whole-genome sequencing approach in a large, population-based cohort with a high HIV infection prevalence and active follow-up. J. Infect. Dis. 211, 1154–1163 (2015).
Cancino-Muñoz, I. et al. Cryptic resistance mutations associated with misdiagnoses of multidrug-resistant tuberculosis. J. Infect. Dis. 220, 316–320 (2019).
Abascal, E. et al. In-depth analysis of a mixed Mycobacterium tuberculosis infection involving a multidrug-resistant strain and a susceptible strain. Clin. Microbiol. Infect. 27, 641–643 (2021).
van Rie, A. et al. Reinfection and mixed infection cause changing Mycobacterium tuberculosis drug-resistance patterns. Am. J. Respir. Crit. Care Med. 172, 636–642 (2005).
Zetola, N. M. et al. Mixed Mycobacterium tuberculosis complex infections and false-negative results for rifampin resistance by GeneXpert MTB/RIF are associated with poor clinical outcomes. J. Clin. Microbiol. 52, 2422–2429 (2014).
Shin, S. S. et al. Mixed Mycobacterium tuberculosis-strain infections are associated with poor treatment outcomes among patients with newly diagnosed tuberculosis, independent of pretreatment heteroresistance. J. Infect. Dis. 218, 1974–1982 (2018).
Cohen, T. et al. Within-host heterogeneity of Mycobacterium tuberculosis infection is associated with poor early treatment response: a prospective cohort study. J. Infect. Dis. 213, 1796–1799 (2016).
Chen, Y. et al. Whole-genome sequencing exhibits better diagnostic performance than variable-number tandem repeats for identifying mixed infections of Mycobacterium tuberculosis. Microbiol. Spectr. 11, e0357022 (2023).
Asare-Baah, M., Séraphin, M. N., Salmon, L. A. T. & Lauzardo, M. Effect of mixed strain infections on clinical and epidemiological features of tuberculosis in Florida. Infect. Genet. Evol. 87, 104659 (2021).
Pandey, P. et al. Mycobacterium tuberculosis polyclonal infections through treatment and recurrence. PLoS ONE 15, e0237345 (2020).
Crowder, R. et al. Impact of heteroresistance on treatment outcomes of people with drug-resistant TB. IJTLD Open 10, 466–472 (2024).
McIvor, A., Koornhof, H. & Kana, B. D. Relapse, re-infection and mixed infections in tuberculosis disease. Pathog. Dis. 75, ftx020 (2017).
Séraphin, M. N. et al. Direct transmission of within-host Mycobacterium tuberculosis diversity to secondary cases can lead to variable between-host heterogeneity without de novo mutation: a genomic investigation. EBioMedicine 47, 293–300 (2019).
Walter, K. S. et al. Signatures of transmission in within-host Mycobacterium tuberculosis complex variation: a retrospective genomic epidemiology study. Lancet Microbe 6, 100936 (2024).
Martin, M. A., Lee, R. S., Cowley, L. A., Gardy, J. L. & Hanage, W. P. Within-host Mycobacterium tuberculosis diversity and its utility for inferences of transmission. Microb. Genom. 4, e000217 (2018).
Lee, R. S., Proulx, J.-F., McIntosh, F., Behr, M. A. & Hanage, W. P. Previously undetected super-spreading of Mycobacterium tuberculosis revealed by deep sequencing. eLife 9, e53245 (2020).
Gabbassov, E., Moreno-Molina, M., Comas, I., Libbrecht, M. & Chindelevitch, L. SplitStrains, a tool to identify and separate mixed Mycobacterium tuberculosis infections from WGS data. Microb. Genom. 7, 000607 (2021).
Votintseva, A. A. et al. Same-day diagnostic and surveillance data for tuberculosis via whole-genome sequencing of direct respiratory samples. J. Clin. Microbiol. 55, 1285–1298 (2017).
Goig, G. A. et al. Whole-genome sequencing of Mycobacterium tuberculosis directly from clinical samples for high-resolution genomic epidemiology and drug resistance surveillance: an observational study. Lancet Microbe 1, e175–e183 (2020).
Doyle, R. M. et al. Direct whole-genome sequencing of sputum accurately identifies drug-resistant Mycobacterium tuberculosis faster than MGIT culture sequencing. J. Clin. Microbiol. 56, e00666–e00718 (2018).
Shockey, A. C., Dabney, J. & Pepperell, C. S. Effects of host, sample, and in vitro culture on genomic diversity of pathogenic mycobacteria. Front. Genet. 10, 460462 (2019).
Mariner-Llicer, C. et al. Genetic diversity within diagnostic sputum samples is mirrored in the culture of Mycobacterium tuberculosis across different settings. Nat. Commun. 15, 7114 (2024).
Genestet, C. et al. Subcultured Mycobacterium tuberculosis isolates on different growth media are fully representative of bacteria within clinical samples. Tuberculosis 116, 61–66 (2019).
Yang, Z. et al. Pangenome graphs in infectious disease: a comprehensive genetic variation analysis of Neisseria meningitidis leveraging Oxford Nanopore long reads. Front. Genet. 14, 1225248 (2023).
Mahairas, G. G., Sabo, P. J., Hickey, M. J., Singh, D. C. & Stover, C. K. Molecular analysis of genetic differences between Mycobacterium bovis BCG and virulent M. bovis. J. Bacteriol. 178, 1274–1282 (1996).
Brosch, R. et al. Comparative genomics uncovers large tandem chromosomal duplications in Mycobacterium bovis BCG Pasteur. Yeast 17, 111–123 (2000).
Domenech, P., Kolly, G. S., Leon-Solis, L., Fallow, A. & Reed, M. B. Massive gene duplication event among clinical isolates of the Mycobacterium tuberculosis W/Beijing family. J. Bacteriol. 192, 4562–4570 (2010).
Shitikov, E. A. et al. Unusual large-scale chromosomal rearrangements in Mycobacterium tuberculosis Beijing B0/W148 cluster isolates. PLoS ONE 9, e84971 (2014).
Karboul, A. et al. Insights into the evolutionary history of tubercle bacilli as disclosed by genetic rearrangements within a PE_PGRS duplicated gene pair. BMC Evol. Biol. 6, 107 (2006).
Merker, M., Kohl, T. A., Niemann, S. & Supply, P. The evolution of strain typing in the Mycobacterium tuberculosis complex. Adv. Exp. Med. Biol. 1019, 43–78 (2017).
Bespiatykh, D., Bespyatykh, J., Mokrousov, I. & Shitikov, E. A comprehensive map of Mycobacterium tuberculosis complex regions of difference. mSphere 6, e0053521 (2021).
Soto, C. Y. et al. IS6110 mediates increased transcription of the phoP virulence gene in a multidrug-resistant clinical isolate responsible for tuberculosis outbreaks. J. Clin. Microbiol. 42, 212–219 (2004).
Behruznia, M. et al. The Mycobacterium tuberculosis complex pangenome is small and driven by sub-lineage-specific regions of difference. eLife https://doi.org/10.1101/2024.03.12.584580 (2024)
Stritt, C. et al. Large contribution of repeats to genetic variation in a transmission cluster of Mycobacterium tuberculosis. Preprint at bioRxiv https://doi.org/10.1101/2024.03.08.584093 (2024).
Wang, L. et al. Multiple genetic paths including massive gene amplification allow to overcome loss of ESX-3 secretion system substrates. Proc. Natl Acad. Sci. USA 119, e2112608119 (2022).
Bolotin, E. & Hershberg, R. Gene loss dominates as a source of genetic variation within clonal pathogenic bacterial species. Genome Biol. Evol. 7, 2173–2187 (2015).
Abrahams, J. S. et al. Towards comprehensive understanding of bacterial genetic diversity: large-scale amplifications in Bordetella pertussis and Mycobacterium tuberculosis. Microb. Genom. 8, 000761 (2022).
Youngblom, M. A., Smith, T. M., Murray, H. J. & Pepperell, C. S. Adaptation of the Mycobacterium tuberculosis transcriptome to biofilm growth. PLoS Pathog. 20, e1012124 (2024).
Reams, A. B. & Roth, J. R. Mechanisms of gene duplication and amplification. Cold Spring Harb. Perspect. Biol. 7, a016592 (2015).
Weiner, B. et al. Independent large scale duplications in multiple M. tuberculosis lineages overlapping the same genomic region. PLoS ONE 7, e26038 (2012).
Kaufmann, S. H. E. Vaccine development against tuberculosis before and after COVID-19. Front. Immunol. 14, 1273938 (2023).
Eldholm, V., Rønning, J. O., Mengshoel, A. T. & Arnesen, T. Import and transmission of Mycobacterium orygis and Mycobacterium africanum, Norway. BMC Infect. Dis. 21, 562 (2021).
Bifani, P. J. et al. Origin and interstate spread of a New York City multidrug-resistant Mycobacterium tuberculosis clone family. JAMA 275, 452–457 (1996).
Namouchi, A., Didelot, X., Schöck, U., Gicquel, B. & Rocha, E. P. C. After the bottleneck: genome-wide diversification of the Mycobacterium tuberculosis complex by mutation, recombination, and natural selection. Genome Res. 22, 721–734 (2012).
Pepperell, C. S. et al. The role of selection in shaping diversity of natural M. tuberculosis populations. PLoS Pathog. 9, e1003543 (2013).
Johri, P. et al. Recommendations for improving statistical inference in population genomics. PLoS Biol. 20, e3001669 (2022).
Rahman, S., Kosakovsky Pond, S. L., Webb, A. & Hey, J. Weak selection on synonymous codons substantially inflates dN/dS estimates in bacteria. Proc. Natl Acad. Sci. USA 118, e2023575118 (2021).
Morales-Arce, A. Y., Harris, R. B., Stone, A. C. & Jensen, J. D. Evaluating the contributions of purifying selection and progeny-skew in dictating within-host Mycobacterium tuberculosis evolution. Evolution 74, 992–1001 (2020).
Walker, T. M. et al. Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study. Lancet Infect. Dis. 13, 137–146 (2013).
Menardo, F. Understanding drivers of phylogenetic clustering and terminal branch lengths distribution in epidemics of Mycobacterium tuberculosis. eLife 11, e76780 (2022).
Stimson, J. et al. Beyond the SNP threshold: identifying outbreak clusters using inferred transmissions. Mol. Biol. Evol. 36, 587–603 (2019).
du Plessis, L. & Stadler, T. Getting to the root of epidemic spread with phylodynamic analysis of genomic data. Trends Microbiol. 23, 383–386 (2015).
Stadler, T. Sampling-through-time in birth–death trees. J. Theor. Biol. 267, 396–404 (2010).
Blount, Z. D., Lenski, R. E. & Losos, J. B. Contingency and determinism in evolution: replaying life’s tape. Science 362, eaam5979 (2018).
Green, A. G. et al. Analysis of genome-wide mutational dependence in naturally evolving Mycobacterium tuberculosis populations. Mol. Biol. Evol. 40, msad131 (2023).
Brunner, V. M. & Fowler, P. W. Compensatory mutations are associated with increased in vitro growth in resistant clinical samples of Mycobacterium tuberculosis. Microb. Genom. 10, 001187 (2024).
Manson, A. L. et al. Genomic analysis of globally diverse Mycobacterium tuberculosis strains provides insights into the emergence and spread of multidrug resistance. Nat. Genet. 49, 395–402 (2017).
Ektefaie, Y., Dixit, A., Freschi, L. & Farhat, M. R. Globally diverse Mycobacterium tuberculosis resistance acquisition: a retrospective geographical and temporal analysis of whole genome sequences. Lancet Microbe 2, e96–e104 (2021).
World Health Organization. Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance, second edition (WHO, 2023).
World Health Organization. Consolidated guidelines on tuberculosis: module 4: treatment: drug-susceptible tuberculosis treatment (WHO, 2022).
Goig, G. A. et al. Transmission as a key driver of resistance to the new tuberculosis drugs. N. Engl. J. Med. 392, 97–99 (2025).
