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The hidden diversity of Mycobacterium tuberculosis complex in Africa: the new L10 and the possible diversification histories of the complex

C Guyeux(2) G Senelle(2) A Le Meur(1) C Sola(1,3) G Refrégier(1)

1:Université Paris-Saclay; 2:CNRS; 3:Université Paris-Cité

Africa is home to all known lineages from Mycobacterium tuberculosis complex (MTBC) including Mycobacterium canettii. Based on the repeated isolation of M. canettii from the Horn of Africa, and the isolation of a recent new lineage with deep branching, L9, this region is usually considered as the cradle of tuberculosis disease. In turn, M. africanum is inferred to have diversified in western Africa. Yet how these two diversification regions may have connected is unknown.

Using the new TB-annotator database, grouping more than 102,000 SRAs, we identified a new lineage branching between L9 and chimpanzee bacilli. We call this new branch L10. It contained only two representatives in TB-annotator. L10 harbours typical features of M. africanum such as absence of RD7-10. L10 strains harbour several distinctive features including a large Region of Deletion encompassing toxin-antitoxin vapB29/vapC29, and synonymous SNPs including gyrA_G7901T, recN_C1920096T, and dnaG_C2621730T. The L10 strains also shared the absence of spacers 7, 9 and  26-43 in standard spoligotyping nomenclature. This feature allowed the identification of a potential third representative of this lineage in SITVIT database.

Interestingly, the only three samples from L10 were all from or in connection with Congo Republic or Democratic Republic of Congo, in central Africa. We further explored the diversity of deeply branching MTBC isolates and their localisation. We discuss the actual diversity of MTBC in Africa and implication on its history of diversification.

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