Phylogenomics of Mycobacterium africanum reveals a new lineage and a complex evolutionary history

Abstract

Human tuberculosis (TB) is caused by members of the Mycobacterium tuberculosis complex (MTBC). The MTBC comprises several human-adapted lineages known as M. tuberculosis sensu stricto , as well as two lineages (L5 and L6) traditionally referred to as Mycobacterium africanum . 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 M. africanum , and highlights the need to consider the particularities of each MTBC lineage for understanding the ecology and epidemiology of TB in Africa and globally.

References 68

1. 1.

   WHO. Global Tuberculosis Report 2019. 2019.

   Not in our library

2. 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.

   Not in our library10.1099/ijsem.0.002507

3. 3.
   A sister lineage of the Mycobacterium tuberculosis complex discovered in the African Great Lakes region · 2020

   No notice
4. 4.
   A New Phylogenetic Framework for the Animal-Adapted Mycobacterium tuberculosis Complex · 2018

   No notice
5. 5.

   Gagneux S. Ecology and evolution of Mycobacterium tuberculosis. Nat Rev Microbiol. 2018;16:202-213.

   Not in our library10.1038/nrmicro.2018.8

6. 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.

   Not in our library10.1073/pnas.0511240103

7. 7.
   Mycobacterial Lineages Causing Pulmonary and Extrapulmonary Tuberculosis, Ethiopia · 2013

   No notice
8. 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.

   Not in our library10.1371/journal.pone.0052841

9. 9.
   Mycobacterium africanum—Review of an Important Cause of Human Tuberculosis in West Africa · 2010

   No notice
10. 10.

    Huet M, Rist N, Boube G, Potier D. Bacteriological study of tuberculosis in Cameroon. Rev Tuberc Pneumol. 1971;35:413-426.

    Not in our library

11. 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.

    Not in our library10.1128/jcm.37.12.3872-3878.1999

12. 12.
    Mycobacterium africanum—Review of an Important Cause of Human Tuberculosis in West Africa · 2010

    No notice
13. 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.

    Not in our library10.1186/1471-2180-8-103

14. 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.

    Not in our library10.1111/j.1574-695x.2009.00628.x

15. 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.

    Not in our library10.1371/journal.pntd.0003370

16. 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.

    Not in our library10.1186/s12879-016-1725-6

17. 17.
    Co‐evolution of M ycobacterium tuberculosis and H omo sapiens · 2015

    No notice
18. 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.

    Not in our library10.1016/j.tube.2008.05.004

19. 19.
    Mycobacterium africanum (Lineage 6) shows slower sputum smear conversion on tuberculosis treatment than Mycobacterium tuberculosis (Lineage 4) in Bamako, Mali. · 2018

    Not checked
20. 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.

    Not in our library10.1128/jcm.35.3.663-666.1997

21. 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.

    Not in our library10.1172/jci11426

22. 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.

    Not in our library10.1093/gbe/evy145

23. 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.

    Not in our library10.1093/infdis/jir883

24. 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.

    Not in our library10.1371/journal.pntd.0002220

25. 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.

    Not in our library10.1016/j.tube.2020.101899

26. 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.

    Not in our library10.1099/jmm.0.000846

27. 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.

    Not in our library10.1086/502977

28. 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.

    Not in our library10.1371/journal.pntd.0004408

29. 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.

    Not in our library10.1016/j.tube.2016.05.014

30. 30.

    Belisle JT, Sonnenberg MG. Isolation of genomic DNA from mycobacteria. Methods Mol Biol. 1998;101:31-44.

    Not in our library10.1385/0-89603-471-2:31

31. 31.
    Trimmomatic: a flexible trimmer for Illumina sequence data · 2014

    No notice
32. 32.

    Li H, Durbin R. Fast and accurate long-read alignment with Burrows–Wheeler transform. Bioinformatics. 2010;26:589-595.

    Not in our library10.1093/bioinformatics/btp698

33. 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.

    Not in our library10.1038/ng.590

34. 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.

    Not in our library10.1093/bioinformatics/btr509

35. 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.

    Not in our library10.1101/gr.129684.111

36. 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.

    Not in our library10.4161/fly.19695

37. 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.

    Not in our library10.1038/ng.3704

38. 38.

    Stamatakis A. RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. Bioinformatics. 2006;22:2688-2690.

    Not in our library10.1093/bioinformatics/btl446

39. 39.

    Lewis PO. A likelihood approach to estimating phylogeny from discrete morphological character data. Syst Biol. 2001;50:913-925.

    Not in our library10.1080/106351501753462876

40. 40.
    Treemmer: a tool to reduce large phylogenetic datasets with minimal loss of diversity · 2018

    No notice

Cited by papers we hold 3

• Pathogenicity and virulence of Mycobacterium tuberculosis · 2023
  No notice
• Population structure, biogeography and transmissibility of Mycobacterium tuberculosis · 2021
  No notice
• Robust barcoding and identification of Mycobacterium tuberculosis lineages for epidemiological and clinical studies · 2020
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.