Origin and Global Expansion of Mycobacterium tuberculosis Complex Lineage 3

Yassir A Shuaib; Christian Utpatel; Thomas A Kohl; Ivan Barilar; Margo Diricks; Nadia Ashraf; Lothar H Wieler; Glennah Kerubo; Eyob A Mesfin; Awa Ba Diallo; Sahal Al-Hajoj; Perpetua Ndung'u; Margaret M Fitzgibbon; Farzam Vaziri; Vitali Sintchenko; Elena Martinez; Sofia O 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 Hoelscher; Andrea Rachow; Andrea Gori; Emmanuel M Tekwu; Larissa K Sidze; Assam A Jean-Paul; Veronique P Beng; Francine Ntoumi; Matthias Frank; Aissatou Gaye Diallo; Souleymane Mboup; Belay Tessema; Dereje Beyene; Sadiq N Khan; Roland Diel; Philip Supply; Florian P Maurer; Harald Hoffmann; Stefan Niemann; Matthias Merker

doi:10.3390/genes13060990

Origin and Global Expansion of Mycobacterium tuberculosis Complex Lineage 3

Genes (Basel). 2022 May 31;13(6):990. doi: 10.3390/genes13060990.

Authors

Yassir A Shuaib^{1

2

3

4}, Christian Utpatel^{2

3}, Thomas A Kohl^{2

3}, Ivan Barilar^{2

3}, Margo Diricks², Nadia Ashraf^{2

3}, Lothar H Wieler^{4

5}, Glennah Kerubo⁶, Eyob A Mesfin⁷, Awa Ba Diallo^{8

9}, Sahal Al-Hajoj^{10

11}, Perpetua Ndung'u¹², Margaret M Fitzgibbon^{13

14}, Farzam Vaziri¹⁵, Vitali Sintchenko^{16

17}, Elena Martinez¹⁶, Sofia O Viegas¹⁸, Yang Zhou¹⁹, Aya Azmy²⁰, Khaled Al-Amry²¹, Sylvain Godreuil²², Mandira Varma-Basil²³, Anshika Narang²³, Solomon Ali²⁴, Patrick Beckert^{2

3}, Viola Dreyer^{2

3}, Mwila Kabwe²⁵, Matthew Bates²⁶, Michael Hoelscher^{27

28}, Andrea Rachow^{27

28}, Andrea Gori²⁹, Emmanuel M Tekwu³⁰, Larissa K Sidze³⁰, Assam A Jean-Paul³⁰, Veronique P Beng³⁰, Francine Ntoumi^{31

32}, Matthias Frank³³, Aissatou Gaye Diallo⁹, Souleymane Mboup⁹, Belay Tessema³⁴, Dereje Beyene³⁵, Sadiq N Khan³⁶, Roland Diel^{37

38}, Philip Supply³⁹, Florian P Maurer^{40

41}, Harald Hoffmann^{42

43}, Stefan Niemann^{2

3}, Matthias Merker^{2

3

44}

Affiliations

¹ College of Veterinary Medicine, Sudan University of Science and Technology, P.O. Box 204 Hilat Kuku, Khartoum North 13321, Sudan.
² Molecular and Experimental Mycobacteriology, Research Center Borstel, 23845 Borstel, Germany.
³ German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, 23845 Borstel, Germany.
⁴ Institute of Microbiology and Epizootics, Freie Universität Berlin, 14163 Berlin, Germany.
⁵ Robert Koch Institute, 13353 Berlin, Germany.
⁶ Department of Medical Microbiology and Parasitology, School of Medicine, Kenyatta University, Nairobi 43844-00100, Kenya.
⁷ Ethiopian Public Health Institute, Addis Ababa 1242, Ethiopia.
⁸ Mycobacteria Unit, Bacteriology-Virology Laboratory, CHU Aristide Le Dantec, Dakar 11000, Senegal.
⁹ Institut de Recherche en Santé de Surveillance Epidemiologique et de Formation (IRESSEF), Diamniadio, Dakar 24600, Senegal.
¹⁰ King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia.
¹¹ College of Medicine, Al Faisal University, Riyadh 11533, Saudi Arabia.
¹² Department of Medical Laboratory Sciences, Jomo Kenyatta University of Agriculture and Technology, Nairobi 62000-00200, Kenya.
¹³ Irish Mycobacteria Reference Laboratory, St James' Hospital, D08 NHY1 Dublin, Ireland.
¹⁴ Department of Clinical Microbiology, Trinity College Dublin, St James's Hospital, D08 NHY1 Dublin, Ireland.
¹⁵ Department of Mycobacteriology and Pulmonary Research, Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran 1316943551, Iran.
¹⁶ Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Sydney 2145, Australia.
¹⁷ Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Sydney 2145, Australia.
¹⁸ Instituto Nacional de Saúde, P.O. Box 1120, Marracuene 1220, Mozambique.
¹⁹ Chinese Center for Disease Control and Prevention, Beijing 102206, China.
²⁰ Central Public Health Laboratories, Clinical Microbiology Department, Ministry of Health, Cairo 11835, Egypt.
²¹ Department of Microbiology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt.
²² Laboratoire de Bactériologie, CHU de Montpellier, MIVEGEC, Université de Montpellier-CNRS-IRD, 34295 Montpellier, France.
²³ Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110007, India.
²⁴ St. Paul's Hospital Millennium Medical College, Addis Ababa 1000, Ethiopia.
²⁵ Department of Pharmacy and Biomedical Science, La Trobe Institute for Molecular Science, La Trobe University, Bendigo 3552, Australia.
²⁶ School of Life and Environmental Sciences, University of Lincoln, Lincoln LN6 7TS, UK.
²⁷ Division of Infectious Diseases and Tropical Medicine, University Hospital, LMU Munich, 80802 Munich, Germany.
²⁸ German Centre for Infection Research (DZIF), Partner Site Munich, 80802 Munich, Germany.
²⁹ Infectious Diseases Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Centre for Multidisciplinary Research in Health Science (MACH), University of Milan, 20122 Milan, Italy.
³⁰ Laboratory for TB Research and Pharmacology, Biotechnology Centre of Nkolbisson, University of Yaoundé I, Yaoundé 8698, Cameroon.
³¹ Faculty of Medicine, Institute for Tropical Medicine, University of Tübingen, 72074 Tübingen, Germany.
³² Fondation Congolaise Pour la Recherche Médicale (FCRM), Villa D6, Campus WHO-AFRO, Brazzaville 2672, Democratic Republic of the Congo.
³³ Allgemeinmedizin, Berliner Ring 39, 72076 Tübingen, Germany.
³⁴ Department of Medical Microbiology, College of Medicine and Health Sciences, University of Gondar, Gondar P.O. Box 196, Ethiopia.
³⁵ Department of Microbial, Cellular and Molecular Biology, Addis Ababa University, Addis Ababa P.O. Box 1176, Ethiopia.
³⁶ Department of Medical Lab Technology, University of Haripur, Haripur 22621, Pakistan.
³⁷ Institute for Epidemiology, University Medical Hospital Schleswig-Holstein, 24105 Kiel, Germany.
³⁸ Lung Clinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), 22927 Großhansdorf, Germany.
³⁹ CNRS, INSERM, CHU Lille, U1019-UMR 9017-CIIL-Center for Infection and Immunity of Lille, Institut Pasteur de Lille, Université de Lille, 59000 Lille, France.
⁴⁰ National and WHO Supranational Reference Center for Mycobacteria, Research Center Borstel, Leibniz Lung Center, 23845 Borstel, Germany.
⁴¹ Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
⁴² Institute of Microbiology and Laboratory Medicine (IML), WHO/GLI-Supranational Reference Laboratory of Tuberculosis, Robert-Koch-Allee 2, 82131 Gauting, Germany.
⁴³ SYNLAB Gauting, SYNLAB MVZ Dachau, 82131 Gauting, Germany.
⁴⁴ Evolution of the Resistome, Research Center Borstel, 23845 Borstel, Germany.

Abstract

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.

Keywords: Lineage 3; MTBC; Mycobacterium tuberculosis; back to Africa.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Genotype
Microbial Sensitivity Tests
Minisatellite Repeats
Mycobacterium tuberculosis* / genetics
Phylogeny

Grants and funding

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.