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
2024-04-19
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