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Origin and Global Expansion of Mycobacterium tuberculosis Complex Lineage 3

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posted on 2022-10-03, 06:48 authored by YA Shuaib, C Utpatel, TA Kohl, I Barilar, M Diricks, N Ashraf, LH Wieler, G Kerubo, EA Mesfin, AB Diallo, S Al-Hajoj, P Ndung’u, MM Fitzgibbon, F Vaziri, V Sintchenko, E Martinez, SO Viegas, Y Zhou, A Azmy, K Al-Amry, S Godreuil, M Varma-Basil, A Narang, S Ali, P Beckert, V Dreyer, Mwila KabweMwila Kabwe, M Bates, M Hoelscher, A Rachow, A Gori, EM Tekwu, LK Sidze, AA Jean-Paul, VP Beng, F Ntoumi, M Frank, AG Diallo, S Mboup, B Tessema, D Beyene, SN Khan, R Diel, P Supply, FP Maurer, H Hoffmann, S Niemann, M Merker
Mycobacterium tuberculosis 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.


Parts of this work have been supported by grants from the European Community’s Seventh Framework Program (FP7/2007–2013) under Grant Agreement No. 278864 in the framework of the EU PathoNGenTrace project and Grant Agreement No. 223681 in the framework of the TB-PAN NET project. The first author is a DAAD (German: Deutscher Akademischer Austauschdienst) or the German Academic Exchange Service stipend recipient, Funding Program No. 57076385. Parts of this work have been supported by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy EXC 22167-390884018, the Leibniz Science Campus EvoLUNG, and the German Center for Infection Research. Part of this work has also been financially supported by CANTAM One- EDCTP Grant N◦ CB.2007.41700.006, offered to the University of Yaoundé I in Cameroon.


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© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (

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