1887

Abstract

(Mtb) lineage 2 (L2) strains are present globally, contributing to a widespread tuberculosis (TB) burden, particularly in Asia where both prevalence of TB and numbers of drug resistant TB are highest. The increasing availability of whole-genome sequencing (WGS) data worldwide provides an opportunity to improve our understanding of the global genetic diversity of Mtb L2 and its association with the disease epidemiology and pathogenesis. However, existing L2 sublineage classification schemes leave >20 % of the Modern Beijing isolates unclassified. Here, we present a revised SNP-based classification scheme of L2 in a genomic framework based on phylogenetic analysis of >4000 L2 isolates from 34 countries in Asia, Eastern Europe, Oceania and Africa. Our scheme consists of over 30 genotypes, many of which have not been described before. In particular, we propose six main genotypes of Modern Beijing strains, denoted L2.2.M1–L2.2.M6. We also provide SNP markers for genotyping L2 strains from WGS data. This fine-scale genotyping scheme, which can classify >98 % of the studied isolates, serves as a basis for more effective monitoring and reporting of transmission and outbreaks, as well as improving genotype-phenotype associations such as disease severity and drug resistance. This article contains data hosted by Microreact.

Funding
This study was supported by the:
  • fogarty international center (Award D43TW009522)
    • Principle Award Recipient: VirasakdiChongsuvivatwong
  • This is an open-access article distributed under the terms of the Creative Commons Attribution NonCommercial License.
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2021-11-17
2021-12-04
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References

  1. Thawornwattana Y, Mahasirimongkol S, Yanai H, Maung H, Cui Z et al. Revised nomenclature and SNP barcode for Mycobacteriumtuberculosis lineage 2. Figshare 2021 [View Article]
    [Google Scholar]
  2. Wiens KE, Woyczynski LP, Ledesma JR, Ross JM, Zenteno-Cuevas R et al. Global variation in bacterial strains that cause tuberculosis disease: A systematic review and meta-analysis. BMC Med 2018; 16:196 [View Article] [PubMed]
    [Google Scholar]
  3. O’Neill MB, Shockey A, Zarley A, Aylward W, Eldholm V et al. Lineage specific histories of Mycobacterium tuberculosis dispersal in Africa and Eurasia. Mol Ecol 2019; 28:3241–3256 [View Article] [PubMed]
    [Google Scholar]
  4. Luo T, Comas I, Luo D, Lu B, Wu J et al. Southern East Asian origin and coexpansion of Mycobacterium tuberculosis Beijing family with Han Chinese. Proc Natl Acad Sci U S A 2015; 112:8136–8141 [View Article] [PubMed]
    [Google Scholar]
  5. Merker M, Blin C, Mona S, Duforet-Frebourg N, Lecher S et al. Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage. Nat Genet 2015; 47:242–249 [View Article] [PubMed]
    [Google Scholar]
  6. Cohen KA, Manson AL, Abeel T, Desjardins CA, Chapman SB et al. Extensive global movement of multidrug-resistant M. tuberculosis strains revealed by whole-genome analysis. Thorax 2019; 74:882–889 [View Article] [PubMed]
    [Google Scholar]
  7. Ribeiro SCM, Gomes LL, Amaral EP, Andrade MRM, Almeida FM et al. Mycobacterium tuberculosis strains of the modern sublineage of the beijing family are more likely to display increased virulence than strains of the ancient sublineage. J Clin Microbiol 2014; 52:2615–2624 [View Article] [PubMed]
    [Google Scholar]
  8. Rajwani R, Yam WC, Zhang Y, Kang Y, Wong BKC et al. Comparative whole-genomic analysis of an ancient L2 lineage Mycobacterium tuberculosis reveals a novel phylogenetic clade and common genetic determinants of hypervirulent strains. Front Cell Infect Microbiol 2017; 7:539 [View Article] [PubMed]
    [Google Scholar]
  9. Holt KE, McAdam P, Thai PVK, Thuong NTT, Ha DTM et al. Frequent transmission of the Mycobacterium tuberculosis Beijing lineage and positive selection for the EsxW Beijing variant in Vietnam. Nat Genet 2018; 50:849–856 [View Article] [PubMed]
    [Google Scholar]
  10. Liu Q, Ma A, Wei L, Pang Y, Wu B et al. China’s tuberculosis epidemic stems from historical expansion of four strains of Mycobacterium tuberculosis. Nat Ecol Evol 2018; 2:1982–1992 [View Article] [PubMed]
    [Google Scholar]
  11. Fine PEM, Crampin AC, Houben R, Mzembe T, Mallard K et al. Large-scale whole genome sequencing of M. tuberculosis provides insights into transmission in a high prevalence area. Elife 2015; 2015:e05166
    [Google Scholar]
  12. Casali N, Nikolayevskyy V, Balabanova Y, Harris SR, Ignatyeva O et al. Evolution and transmission of drug-resistant tuberculosis in a Russian population. Nat Genet 2014; 46:279–286 [View Article] [PubMed]
    [Google Scholar]
  13. Eldholm V, Pettersson JHO, Brynildsrud OB, Kitchen A, Rasmussen EM et al. Armed conflict and population displacement as drivers of the evolution and dispersal of Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 2016; 113:13881–13886 [View Article] [PubMed]
    [Google Scholar]
  14. Tsolaki AG, Gagneux S, Pym AS, Goguet De La Salmoniere YOL, Kreiswirth BN et al. Genomic deletions classify the Beijing/W strains as a distinct genetic lineage of Mycobacterium tuberculosis. J Clin Microbiol 2005; 43:3185–3191 [View Article] [PubMed]
    [Google Scholar]
  15. Smittipat N, Billamas P, Palittapongarnpim M, Thong-On A, Temu MM et al. Polymorphism of variable-number tandem repeats at multiple loci in Mycobacterium tuberculosis. J Clin Microbiol 2005; 43:5034–5043 [View Article] [PubMed]
    [Google Scholar]
  16. 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]
  17. Ebrahimi-Rad M, Bifani P, Martin C, Kremer K, Samper S et al. Mutations in putative mutator genes of Mycobacterium tuberculosis strains of the W-Beijing family. Emerg Infect Dis 2003; 9:838–845 [View Article] [PubMed]
    [Google Scholar]
  18. Filliol I, Motiwala AS, Cavatore M, Qi W, Hazbón MH et al. Global phylogeny of Mycobacterium tuberculosis based on single nucleotide polymorphism (SNP) analysis: Insights into tuberculosis evolution, phylogenetic accuracy of other DNA fingerprinting systems, and recommendations for a minimal standard SNP set. J Bacteriol 2006; 188:759–772 [View Article] [PubMed]
    [Google Scholar]
  19. Mestre O, Luo T, Dos Vultos T, Kremer K, Murray A et al. Phylogeny of Mycobacterium tuberculosis Beijing strains constructed from Polymorphisms in genes involved in DNA replication, recombination and repair. PLoS One 2011; 6:e16020 [View Article] [PubMed]
    [Google Scholar]
  20. Coscolla M, Gagneux S. Consequences of genomic diversity in Mmycobacterium tuberculosis. Semin Immunol 2014; 26:431–444 [View Article] [PubMed]
    [Google Scholar]
  21. Zhang H, Li D, Zhao L, Fleming J, Lin N et al. Genome sequencing of 161 Mycobacterium tuberculosis isolates from China identifies genes and intergenic regions associated with drug resistance. Nat Genet 2013; 45:1255–1260 [View Article] [PubMed]
    [Google Scholar]
  22. Coll F, McNerney R, Guerra-Assunção JA, Glynn JR, Perdigão J et al. A robust SNP barcode for typing Mycobacterium tuberculosis complex strains. Nat Commun 2014; 5:4812 [View Article] [PubMed]
    [Google Scholar]
  23. Mokrousov I, Narvskaya O, Otten T, Vyazovaya A, Limeschenko E et al. Phylogenetic reconstruction within Mycobacterium tuberculosis Beijing genotype in northwestern Russia. Res Microbiol 2002; 153:629–637 [View Article] [PubMed]
    [Google Scholar]
  24. Plikaytis BB, Marden JL, Crawford JT, Woodley CL, Butler WR et al. Multiplex PCR assay specific for the multidrug-resistant strain W of Mycobacterium tuberculosis. J Clin Microbiol 1994; 32:1542–1546
    [Google Scholar]
  25. Mokrousov I, Ho ML, Otten T, Nguyen NL, Vyshnevskyi B et al. Origin and primary dispersal of the Mycobacterium tuberculosis Beijing genotype: Clues from human phylogeography. Genome Res 2005; 15:1357–1364 [View Article] [PubMed]
    [Google Scholar]
  26. Shitikov E, Kolchenko S, Mokrousov I, Bespyatykh J, Ischenko D et al. Evolutionary pathway analysis and unified classification of East Asian lineage of Mycobacterium tuberculosis. Sci Rep 2017; 7:9227 [View Article] [PubMed]
    [Google Scholar]
  27. Liu Q, Luo T, Dong X, Sun G, Liu Z et al. Genetic features of Mycobacterium tuberculosis modern Beijing sublineage. Emerg Microbes Infect 2016; 5:e14
    [Google Scholar]
  28. Napier G, Campino S, Merid Y, Abebe M, Woldeamanuel Y et al. Robust barcoding and identification of Mycobacterium tuberculosis lineages for epidemiological and clinical studies. Genome Med 2020; 12:114 [View Article] [PubMed]
    [Google Scholar]
  29. Ajawatanawong P, Yanai H, Smittipat N, Disratthakit A, Yamada N et al. A novel Ancestral Beijing sublineage of Mycobacterium tuberculosis suggests the transition site to Modern Beijing sublineages. Sci Rep 2019; 9:13718 [View Article] [PubMed]
    [Google Scholar]
  30. Rutaihwa LK, Menardo F, Stucki D, Gygli SM, Ley SD et al. Multiple introductions of Mycobacterium tuberculosis Lineage 2-Beijing into Africa over centuries. Front Ecol Evol 2019; 7:112 [View Article]
    [Google Scholar]
  31. Bolger AM, Lohse M, Usadel B. Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics 2014; 30:2114–2120 [View Article] [PubMed]
    [Google Scholar]
  32. Li H. Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. ARXIV; 2013 http://arxiv.org/abs/1303.3997
  33. Poplin R, Ruano-Rubio V, DePristo MA, Fennell TJ, Carneiro MO et al. Scaling accurate genetic variant discovery to tens of thousands of samples. bioRxiv Preprint 2018 [View Article]
    [Google Scholar]
  34. 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 (Austin) 2012; 6:80–92 [View Article] [PubMed]
    [Google Scholar]
  35. Klopper M, Heupink TH, Hill-Cawthorne G, Streicher EM, Dippenaar A et al. A landscape of genomic alterations at the root of a near-untreatable tuberculosis epidemic. BMC Med 2020; 18:24 [View Article] [PubMed]
    [Google Scholar]
  36. Xia E, Teo YY, Ong RTH. SpoTyping: Fast and accurate in silico Mycobacterium spoligotyping from sequence reads. Genome Med 2016; 8:19 [View Article] [PubMed]
    [Google Scholar]
  37. Page A, Alikhan N-F, Strinden M, Le Viet T, Skvortsov T. Rapid Mycobacterium tuberculosis spoligotyping from uncorrected long reads using Galru. bioRxiv 2020
    [Google Scholar]
  38. Minh BQ, Schmidt HA, Chernomor O, Schrempf D, Woodhams MD et al. IQ-TREE 2: new models and efficient methods for phylogenetic inference in the genomic era. Mol Biol Evol 2020; 37:1530–1534 [View Article] [PubMed]
    [Google Scholar]
  39. Kalyaanamoorthy S, Minh BQ, Wong TKF, Von Haeseler A, Jermiin LS. ModelFinder: Fast model selection for accurate phylogenetic estimates. Nat Methods 2017; 14:587–589 [View Article] [PubMed]
    [Google Scholar]
  40. Walker TM, Ip CLC, Harrell RH, Evans JT, Kapatai G et al. Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: A retrospective observational study. Lancet Infect Dis 2013; 13:137–146 [View Article] [PubMed]
    [Google Scholar]
  41. Yang C, Luo T, Shen X, Wu J, Gan M et al. Transmission of multidrug-resistant Mycobacterium tuberculosis in Shanghai, China: a retrospective observational study using whole-genome sequencing and epidemiological investigation. Lancet Infect Dis 2017; 17:275–284 [View Article] [PubMed]
    [Google Scholar]
  42. Bhatia G, Patterson N, Sankararaman S, Price AL. Estimating and interpreting FST: The impact of rare variants. Genome Res 2013; 23:1514–1521 [View Article] [PubMed]
    [Google Scholar]
  43. Miles A, Harding NJ. Scikit-allel. Zenodo 2017
    [Google Scholar]
  44. DeJesus MA, Gerrick ER, Xu W, Park SW, Long JE et al. Comprehensive essentiality analysis of the Mycobacterium tuberculosis genome via saturating transposon mutagenesis. mBio 2017; 8:e02133-16 [View Article]
    [Google Scholar]
  45. 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] [PubMed]
    [Google Scholar]
  46. Vita R, Mahajan S, Overton JA, Dhanda SK, Martini S et al. The Immune Epitope Database (IEDB): 2018 update. Nucleic Acids Res 2019; 47:43 [View Article]
    [Google Scholar]
  47. Mokrousov I, Sinkov V, Vyazovaya A, Pasechnik O, Solovieva N et al. Genomic signatures of drug resistance in highly resistant Mycobacterium tuberculosis strains of the early ancient sublineage of Beijing genotype in Russia. Int J Antimicrob Agents 2020; 56:106036 [View Article] [PubMed]
    [Google Scholar]
  48. Han SJ, Song T, Cho Y-J, Kim J-S, Choi SY et al. Complete genome sequence of Mycobacterium tuberculosis K from a Korean high school outbreak, belonging to the Beijing family. Stand Genomic Sci 2015; 10:78 [View Article] [PubMed]
    [Google Scholar]
  49. Mokrousov I, Vyazovaya A, Pasechnik O, Gerasimova A, Dymova M et al. Early ancient sublineages of Mycobacterium tuberculosis Beijing genotype: unexpected clues from phylogenomics of the pathogen and human history. Clin Microbiol Infect 2019; 25:1039 [View Article] [PubMed]
    [Google Scholar]
  50. Regmi SM, Chaiprasert A, Kulawonganunchai S, Tongsima S, Coker OO et al. Whole genome sequence analysis of multidrug-resistant Mycobacterium tuberculosis Beijing isolates from an outbreak in Thailand. Mol Genet Genomics 2015; 290:1933–1941 [View Article] [PubMed]
    [Google Scholar]
  51. Bifani PJ, Mathema B, Kurepina NE, Kreiswirth BN. Global dissemination of the Mycobacterium tuberculosis W-Beijing family strains. Trends Microbiol 2002; 10:45–52 [View Article] [PubMed]
    [Google Scholar]
  52. Mokrousov I. Insights into the origin, emergence, and current spread of a successful Russian clone of Mycobacterium tuberculosis. Clin Microbiol Rev 2013; 26:342–360 [View Article] [PubMed]
    [Google Scholar]
  53. Shitikov E, Vyazovaya A, Malakhova M, Guliaev A, Bespyatykh J et al. Simple assay for detection of the Central Asia outbreak clade of the Mycobacterium tuberculosis Beijing genotype. J Clin Microbiol 2019; 57:e00215-19 [View Article]
    [Google Scholar]
  54. Mokrousov I, Chernyaeva E, Vyazovaya A, Skiba Y, Solovieva N et al. Rapid assay for detection of the epidemiologically important Central Asian/Russian strain of the Mycobacterium tuberculosis Beijing genotype. J Clin Microbiol 2018; 56:e01551-17 [View Article] [PubMed]
    [Google Scholar]
  55. Merker M, Barbier M, Cox H, Rasigade JP, Feuerriegel S et al. Compensatory evolution drives multidrug-resistant tuberculosis in central Asia. Elife 2018; 7:e38200 [View Article] [PubMed]
    [Google Scholar]
  56. Tantivitayakul P, Ruangchai W, Juthayothin T, Smittipat N, Disratthakit A et al. Homoplastic single nucleotide polymorphisms contributed to phenotypic diversity in Mycobacterium tuberculosis. Sci Rep 2020; 10:8024 [View Article] [PubMed]
    [Google Scholar]
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