1887

Abstract

Human tuberculosis (TB) is caused by members of the complex (MTBC). The MTBC comprises several human-adapted lineages known as , as well as two lineages (L5 and L6) traditionally referred to as . Strains of L5 and L6 are largely limited to West Africa for reasons unknown, and little is known of their genomic diversity, phylogeography and evolution. Here, we analysed the genomes of 350 L5 and 320 L6 strains, isolated from patients from 21 African countries, plus 5 related genomes that had not been classified into any of the known MTBC lineages. Our population genomic and phylogeographical analyses showed that the unclassified genomes belonged to a new group that we propose to name MTBC lineage 9 (L9). While the most likely ancestral distribution of L9 was predicted to be East Africa, the most likely ancestral distribution for both L5 and L6 was the Eastern part of West Africa. Moreover, we found important differences between L5 and L6 strains with respect to their phylogeographical substructure and genetic diversity. Finally, we could not confirm the previous association of drug-resistance markers with lineage and sublineages. Instead, our results indicate that the association of drug resistance with lineage is most likely driven by sample bias or geography. In conclusion, our study sheds new light onto the genomic diversity and evolutionary history of , and highlights the need to consider the particularities of each MTBC lineage for understanding the ecology and epidemiology of TB in Africa and globally.

Funding
This study was supported by the:
  • Ministerio de Ciencia, Innovación y Universidades (Award Ramon y Cajal)
    • Principle Award Recipient: Mireia Coscollá
  • H2020 European Research Council (Award 883582-ECOEVODRTB)
    • Principle Award Recipient: Sebastien Gagneux
  • European Society of Clinical Microbiology and Infectious Diseases
    • Principle Award Recipient: Mireia Coscollá
  • Conselleria d'Educació, Investigació, Cultura i Esport (Award SEJI/2019/011)
    • Principle Award Recipient: Mireia Coscollá
  • Ministerio de Ciencia, Innovación y Universidades (Award RTI2018-094399-A-I00)
    • Principle Award Recipient: Mireia Coscollá
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Award 310030_188888, IZRJZ3_164171, IZLSZ3_170834 and CRSII5_177163)
    • Principle Award Recipient: Sebastien Gagneux
  • Wellcome Trust (Award 097134/Z/11/Z)
    • Principle Award Recipient: Dorothy Yeboah-Manu
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2021-02-08
2021-10-17
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References

  1. WHO Global Tuberculosis Report 2019. Geneva: World Health Organization; 2019ISBN 978-92-4-156571-4
  2. Riojas MA, McGough KJ, Rider-Riojas CJ, Rastogi N, Hazbón MH. Phylogenomic analysis of the species of the Mycobacterium tuberculosis complex demonstrates that Mycobacterium africanum, Mycobacterium bovis, Mycobacterium caprae, Mycobacterium microti and Mycobacterium pinnipedii are later heterotypic synonyms of Mycobacterium tuberculosis . Int J Syst Evol Microbiol 2018; 68:324–332 [View Article]
    [Google Scholar]
  3. Ngabonziza JCS, Loiseau C, Marceau M, Jouet A, Menardo F et al. A sister lineage of the Mycobacterium tuberculosis complex discovered in the African Great Lakes region. Nat Commun 2020; 11:2917 [View Article]
    [Google Scholar]
  4. Brites D, Loiseau C, Menardo F, Borrell S, Boniotti MB et al. A vew phylogenetic framework for the animal-adapted Mycobacterium tuberculosis complex. Front Microbiol 2018; 9:2820 [View Article]
    [Google Scholar]
  5. Gagneux S. Ecology and evolution of Mycobacterium tuberculosis . Nat Rev Microbiol 2018; 16:202–213 [View Article]
    [Google Scholar]
  6. Gagneux S, DeRiemer K, Van T, Kato-Maeda M, de Jong BC et al. Variable host-pathogen compatibility in Mycobacterium tuberculosis . Proc Natl Acad Sci USA 2006; 103:2869–2873 [View Article]
    [Google Scholar]
  7. Firdessa R, Berg S, Hailu E, Schelling E, Gumi B et al. Mycobacterial lineages causing pulmonary and extrapulmonary tuberculosis, Ethiopia. Emerg Infect Dis 2013; 19:460–463 [View Article]
    [Google Scholar]
  8. Blouin Y, Hauck Y, Soler C, Fabre M, Vong R et al. Significance of the identification in the Horn of Africa of an exceptionally deep branching Mycobacterium tuberculosis clade. PLoS One 2012; 7:e52841 [View Article]
    [Google Scholar]
  9. de Jong BC, Antonio M, Gagneux S. Mycobacterium africanum – review of an important cause of human tuberculosis in West Africa. PLoS Negl Trop Dis 2010; 4:e744 [View Article]
    [Google Scholar]
  10. Huet M, Rist N, Boube G, Potier D. Bacteriological study of tuberculosis in Cameroon. Rev Tuberc Pneumol 1971; 35:413–426
    [Google Scholar]
  11. Källenius G, Koivula T, Ghebremichael S, Hoffner SE, Norberg R et al. Evolution and clonal traits of Mycobacterium tuberculosis complex in Guinea-Bissau. J Clin Microbiol 1999; 37:3872–3878 [View Article]
    [Google Scholar]
  12. de Jong BC, Antonio M, Gagneux S. Mycobacterium africanum – review of an important cause of human tuberculosis in West Africa. PLoS Negl Trop Dis 2010; 4:e744 [View Article][PubMed]
    [Google Scholar]
  13. Homolka S, Post E, Oberhauser B, George A, Westman L et al. High genetic diversity among Mycobacterium tuberculosis complex strains from Sierra Leone. BMC Microbiol 2008; 8:103 [View Article]
    [Google Scholar]
  14. de Jong BC, Adetifa I, Walther B, Hill PC, Antonio M et al. Differences between tuberculosis cases infected with Mycobacterium africanum, West African type 2, relative to Euro-American Mycobacterium tuberculosis: an update. FEMS Immunol Med Microbiol 2010; 58:102–105 [View Article][PubMed]
    [Google Scholar]
  15. Asante-Poku A, Yeboah-Manu D, Otchere ID, Aboagye SY, Stucki D et al. Mycobacterium africanum is associated with patient ethnicity in Ghana. PLoS Negl Trop Dis 2015; 9:e3370 [View Article]
    [Google Scholar]
  16. Asante-Poku A, Otchere ID, Osei-Wusu S, Sarpong E, Baddoo A et al. Molecular epidemiology of Mycobacterium africanum in Ghana. BMC Infect Dis 2016; 16:385 [View Article]
    [Google Scholar]
  17. Brites D, Gagneux S. Co-evolution of Mycobacterium tuberculosis and Homo sapiens . Immunol Rev 2015; 264:6–24 [View Article][PubMed]
    [Google Scholar]
  18. Meyer CG, Scarisbrick G, Niemann S, Browne EN, Chinbuah MA et al. Pulmonary tuberculosis: virulence of Mycobacterium africanum and relevance in HIV co-infection. Tuberculosis 2008; 88:482–489 [View Article]
    [Google Scholar]
  19. Diarra B, Kone M, Togo ACG, Sarro YDS, Cisse AB et al. Mycobacterium africanum (lineage 6) shows slower sputum smear conversion on tuberculosis treatment than Mycobacterium tuberculosis (lineage 4) in Bamako, Mali. PLoS One 2018; 13:e0208603 [View Article]
    [Google Scholar]
  20. Haas WH, Bretzel G, Amthor B, Schilke K, Krommes G et al. Comparison of DNA fingerprint patterns of isolates of Mycobacterium africanum from East and West Africa. J Clin Microbiol 1997; 35:663–666 [View Article]
    [Google Scholar]
  21. Kato-Maeda M, Bifani PJ, Kreiswirth BN, Small PM. The nature and consequence of genetic variability within Mycobacterium tuberculosis . J Clin Invest 2001; 107:533–537 [View Article][PubMed]
    [Google Scholar]
  22. Ates LS, Dippenaar A, Sayes F, Pawlik A, Bouchier C et al. Unexpected genomic and phenotypic diversity of Mycobacterium africanum lineage 5 affects drug resistance, protein secretion, and immunogenicity. Genome Biol Evol 2018; 10:1858–1874 [View Article]
    [Google Scholar]
  23. Bold TD, Davis DC, Penberthy KK, Cox LM, Ernst JD et al. Impaired fitness of Mycobacterium africanum despite secretion of ESAT-6. J Infect Dis 2012; 205:984–990 [View Article][PubMed]
    [Google Scholar]
  24. Gehre F, Otu J, DeRiemer K, de Sessions PF, Hibberd ML et al. Deciphering the growth behaviour of Mycobacterium africanum . PLoS Negl Trop Dis 2013; 7:e2220 [View Article]
    [Google Scholar]
  25. Ofori-Anyinam B, Riley AJ, Jobarteh T, Gitteh E, Sarr B et al. Comparative genomics shows differences in the electron transport and carbon metabolic pathways of Mycobacterium africanum relative to Mycobacterium tuberculosis and suggests an adaptation to low oxygen tension. Tuberculosis 2020; 120:101899 [View Article]
    [Google Scholar]
  26. Sanoussi C N'Dira, de Jong BC, Odoun M, Arekpa K, Ali Ligali M et al. Low sensitivity of the MPT64 identification test to detect lineage 5 of the Mycobacterium tuberculosis complex. J Med Microbiol 2018; 67:1718–1727 [View Article][PubMed]
    [Google Scholar]
  27. de Jong BC, Hill PC, Brookes RH, Gagneux S, Jeffries DJ et al. Mycobacterium africanum elicits an attenuated T cell response to early secreted antigenic target, 6 kDa, in patients with tuberculosis and their household contacts. J Infect Dis 2006; 193:1279–1286 [View Article]
    [Google Scholar]
  28. Gehre F, Kumar S, Kendall L, Ejo M, Secka O et al. A mycobacterial perspective on tuberculosis in West Africa: significant geographical variation of M. africanum and other M. tuberculosis complex lineages. PLoS Negl Trop Dis 2016; 10:e0004408 [View Article]
    [Google Scholar]
  29. Otchere ID, Asante-Poku A, Osei-Wusu S, Baddoo A, Sarpong E et al. Detection and characterization of drug-resistant conferring genes in Mycobacterium tuberculosis complex strains: a prospective study in two distant regions of Ghana. Tuberculosis 2016; 99:147–154 [View Article]
    [Google Scholar]
  30. Belisle JT, Sonnenberg MG. Isolation of genomic DNA from mycobacteria. Methods Mol Biol 1998; 101:31–44
    [Google Scholar]
  31. Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 2014; 30:2114–2120 [View Article]
    [Google Scholar]
  32. Li H, Durbin R. Fast and accurate long-read alignment with Burrows–Wheeler transform. Bioinformatics 2010; 26:589–595 [View Article]
    [Google Scholar]
  33. Comas I, Chakravartti J, Small PM, Galagan J, Niemann S et al. Human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved. Nat Genet 2010; 42:498–503 [View Article]
    [Google Scholar]
  34. Li H. A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data. Bioinformatics 2011; 27:2987–2993 [View Article]
    [Google Scholar]
  35. Koboldt DC, Zhang Q, Larson DE, Shen D, McLellan MD et al. VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res 2012; 22:568–576 [View Article]
    [Google Scholar]
  36. Cingolani P, Platts A, Wang LL, Coon M, Nguyen T et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly 2012; 6:80–92 [View Article][PubMed]
    [Google Scholar]
  37. Stucki D, Brites D, Jeljeli L, Coscolla M, Liu Q et al. Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages. Nat Genet 2016; 48:1535–1543 [View Article]
    [Google Scholar]
  38. Stamatakis A. RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. Bioinformatics 2006; 22:2688–2690 [View Article]
    [Google Scholar]
  39. Lewis PO. A likelihood approach to estimating phylogeny from discrete morphological character data. Syst Biol 2001; 50:913–925 [View Article]
    [Google Scholar]
  40. Menardo F, Loiseau C, Brites D, Coscolla M, Gygli SM et al. Treemmer: a tool to reduce large phylogenetic datasets with minimal loss of diversity. BMC Bioinformatics 2018; 19:164 [View Article]
    [Google Scholar]
  41. Guangchuang Y, SD K, Huachen Z, Yi G, Tsan-Yuk LT. ggtree: an R package for visualization and annotation of phylogenetic trees with their covariates and other associated data. Methods Ecol Evol 2017; 8:28–36
    [Google Scholar]
  42. R Core Team R: a language and environment for statistical computing Vienna: R Foundation for Statistical Computing; 2018
    [Google Scholar]
  43. Yu Y, Harris AJ, Blair C, He X. RASP (reconstruct ancestral state in phylogenies): a tool for historical biogeography. Mol Phylogenet Evol 2015; 87:46–49 [View Article]
    [Google Scholar]
  44. Excoffier L, Laval G, Schneider S. Arlequin (version 3.0): an integrated software package for population genetics data analysis. Evol Bioinform 2005; 1:47–50 [View Article]
    [Google Scholar]
  45. Paradis E, Claude J, Strimmer K. APE: Analyses of Phylogenetics and Evolution in R language. Bioinformatics 2004; 20:289–290 [View Article]
    [Google Scholar]
  46. Hartl DL, Clarck AG. Principles of Population Genetics Sunderland, MA: Sinauer Associates; 2006
    [Google Scholar]
  47. Jombart T. Adegenet: a R package for the multivariate analysis of genetic markers. Bioinformatics 2008; 24:1403–1405 [View Article]
    [Google Scholar]
  48. Parks DH, Mankowski T, Zangooei S, Porter MS, Armanini DG et al. GenGIS 2: geospatial analysis of traditional and genetic biodiversity, with new gradient algorithms and an extensible plugin framework. PLoS One 2013; 8:e69885 [View Article]
    [Google Scholar]
  49. Couvin D, David A, Zozio T, Rastogi N. Macro-geographical specificities of the prevailing tuberculosis epidemic as seen through SITVIT2, an updated version of the Mycobacterium tuberculosis genotyping database. Infect Genet Evol 2019; 72:31–43 [View Article][PubMed]
    [Google Scholar]
  50. Payne JL, Menardo F, Trauner A, Borrell S, Gygli SM et al. Transition bias influences the evolution of antibiotic resistance in Mycobacterium tuberculosis . PLoS Biol 2019; 17:e3000265 [View Article]
    [Google Scholar]
  51. Lipworth S, Jajou R, de Neeling A, Bradley P, van der Hoek W et al. SNP-IT tool for identifying subspecies and associated lineages of Mycobacterium tuberculosis complex. Emerg Infect Dis 2019; 25:482–488 [View Article]
    [Google Scholar]
  52. Ngabonziza JCS, Loiseau C, Marceau M, Jouet A, Menardo F et al. A sister lineage of the Mycobacterium tuberculosis complex discovered in the African Great Lakes region. Nat Commun 2020; 11:2917 [View Article][PubMed]
    [Google Scholar]
  53. Borrell S, Trauner A, Brites D, Rigouts L, Loiseau C et al. Reference set of Mycobacterium tuberculosis clinical strains: a tool for research and product development. PLoS One 2019; 14:e0214088 [View Article]
    [Google Scholar]
  54. Brosch R, Gordon SV, Marmiesse M, Brodin P, Buchrieser C et al. A new evolutionary scenario for the Mycobacterium tuberculosis complex. Proc Natl Acad Sci USA 2002; 99:3684–3689 [View Article]
    [Google Scholar]
  55. Mostowy S, Cousins D, Brinkman J, Aranaz A, Behr MA. Genomic deletions suggest a phylogeny for the Mycobacterium tuberculosis complex. J Infect Dis 2002; 186:74–80 [View Article]
    [Google Scholar]
  56. Wright S. Genetical structure of populations. Nature 1950; 166:247–249 [View Article]
    [Google Scholar]
  57. Otchere ID, Coscollá M, Sánchez-Busó L, Asante-Poku A, Brites D et al. Comparative genomics of Mycobacterium africanum lineage 5 and lineage 6 from Ghana suggests distinct ecological niches. Sci Rep 2018; 8:11269 [View Article]
    [Google Scholar]
  58. Mostowy S, Onipede A, Gagneux S, Niemann S, Kremer K et al. Genomic analysis distinguishes Mycobacterium africanum . J Clin Microbiol 2004; 42:3594–3599 [View Article][PubMed]
    [Google Scholar]
  59. Hershberg R, Lipatov M, Small PM, Sheffer H, Niemann S et al. High functional diversity in Mycobacterium tuberculosis driven by genetic drift and human demography. PLoS Biol 2008; 6:e311 [View Article][PubMed]
    [Google Scholar]
  60. Supply P, Marceau M, Mangenot S, Roche D, Rouanet C et al. Genomic analysis of smooth tubercle bacilli provides insights into ancestry and pathoadaptation of Mycobacterium tuberculosis . Nat Genet 2013; 45:172–179 [View Article]
    [Google Scholar]
  61. Comas I, Coscolla M, Luo T, Borrell S, Holt KE et al. Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans. Nat Genet 2013; 45:1176–1182 [View Article]
    [Google Scholar]
  62. N'Dira Sanoussi C, Coscolla M, Ofori-Anyinam B, Otchere ID, Antonio M et al. Mycobacterium tuberculosis complex lineage 5 exhibits high levels of within-lineage genomic diversity and differing gene content compared to the type strain H37Rv. bioRxiv 2020164186
    [Google Scholar]
  63. Coscolla M, Copin R, Sutherland J, Gehre F, de Jong B et al. M. tuberculosis T cell epitope analysis reveals paucity of antigenic variation and identifies rare variable TB antigens. Cell Host Microbe 2015; 18:538–548 [View Article][PubMed]
    [Google Scholar]
  64. Lindestam Arlehamn CS, Paul S, Mele F, Huang C, Greenbaum JA et al. Immunological consequences of intragenus conservation of Mycobacterium tuberculosis T-cell epitopes. Proc Natl Acad Sci USA 2015; 112:E147–E155 [View Article]
    [Google Scholar]
  65. Ernst JD. The immunological life cycle of tuberculosis. Nat Rev Immunol 2012; 12:581–591 [View Article]
    [Google Scholar]
  66. Hlavsa MC, Moonan PK, Cowan LS, Navin TR, Kammerer JS et al. Human tuberculosis due to Mycobacterium bovis in the United States, 1995-2005. Clin Infect Dis 2008; 47:168–175 [View Article][PubMed]
    [Google Scholar]
  67. Park D, Qin H, Jain S, Preziosi M, Minuto JJ et al. Tuberculosis due to Mycobacterium bovis in patients coinfected with human immunodeficiency virus. Clin Infect Dis 2010; 51:1343–1346 [View Article][PubMed]
    [Google Scholar]
  68. de Jong BC, Hill PC, Brookes RH, Otu JK, Peterson KL et al. Mycobacterium africanum: a new opportunistic pathogen in HIV infection?. AIDS 2005; 19:1714–1715 [View Article][PubMed]
    [Google Scholar]
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