Origin and Global Expansion of Mycobacterium tuberculosis Complex Lineage 3
Yassir Adam Shuaib, Christian Utpatel, Thomas A. Kohl, Ivan Barilar, Margo Diricks, Nadia Ashraf, Lothar H. Wieler, Glennah Kerubo, Eyob Abera Mesfin, Awa Ba-Diallo, Sahal Al‐Hajoj, Perpetua Ndung’u, Margaret Fitzgibbon, Farzam Vaziri, Vitali Sintchenko, Elena Martínez, Sofía Viegas, Yang Zhou, Aya Azmy, Khaled Al-Amry, Sylvain Godreuil, Mandira Varma‐Basil, Anshika Narang, Solomon Ali, Patrick Beckert, Viola Dreyer, Mwila Kabwe, Matthew Bates, Michael Höelscher, Andrea Rachow, Andrea Gori, Emmanuel Mouafo Tekwu, Larissa Kamgue Sidze, Assam A. Jean-Paul, Véronique Penlap Beng, Francine Ntoumi, Matthias Frank, Aïssatou Gaye Diallo, Souleymane Mboup, Belay Tessema, Dereje Beyene, Sadiq Noor Khan, Roland Diel, Philip Supply, Florian P. Maurer, Harald Hoffmann, Stefan Niemann, Matthias Merker
Abstract
complex (MTBC) Lineage 3 (L3) strains are abundant in world regions with the highest tuberculosis burden. To investigate the population structure and the global diversity of this major lineage, we analyzed a dataset comprising 2682 L3 strains from 38 countries over 5 continents, by employing 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats genotyping (MIRU-VNTR) and drug susceptibility testing. We further combined whole-genome sequencing (WGS) and phylogeographic analysis for 373 strains representing the global L3 genetic diversity. Ancestral state reconstruction confirmed that the origin of L3 strains is located in Southern Asia and further revealed multiple independent introduction events into North-East and East Africa. This study provides a systematic understanding of the global diversity of L3 strains and reports phylogenetic variations that could inform clinical trials which evaluate the effectivity of new drugs/regimens or vaccine candidates.