Fabrizio Menardo1,2, Liliana K Rutaihwa1,2, Michaela Zwyer1,2, Sonia Borrell1,2, Iñaki Comas3, Emilyn Costa Conceição4,5, Mireia Coscolla6, Helen Cox7, Moses Joloba8, Horng-Yunn Dou9, Julia Feldmann1,2, Lukas Fenner1,2,10, Janet Fyfe11, Qian Gao12, Darío García de Viedma13,14,15, Alberto L Garcia-Basteiro16,17, Sebastian M Gygli1,2, Jerry Hella1,2,18, Hellen Hiza1,2, Levan Jugheli1,2, Lujeko Kamwela1,2,18, Midori Kato-Maeda19, Qingyun Liu12, Serej D Ley1,2,20, Chloe Loiseau1,2, Surakameth Mahasirimongkol21,22, Bijaya Malla1,2, Prasit Palittapongarnpim21,22, Niaina Rakotosamimanana23, Voahangy Rasolofo23, Miriam Reinhard1,2, Klaus Reither2,24, Mohamed Sasamalo1,2,18, Rafael Silva Duarte4, Christophe Sola25,26, Philip Suffys27, Karla Valeria Batista Lima28,29, Dorothy Yeboah-Manu30, Christian Beisel31, Daniela Brites1,2, Sebastien Gagneux1,2. 1. Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland. 2. University of Basel, Basel, Switzerland. 3. Institute of Biomedicine of Valencia, Valencia, Spain. 4. Instituto de Microbiologia, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. 5. Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. 6. I2SysBio, University of Valencia, Valencia, Spain. 7. Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa. 8. Department of Medical Microbiology, Makerere University, Kampala, Uganda. 9. National Institute of Infectious Diseases and Vaccinology, National Health Research Institute, Zhunan, Taiwan. 10. Institute for Social and Preventive Medicine, University of Bern, Bern, Switzerland. 11. Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia. 12. Institute of Medical Microbiology, School of Basic Medical Science of Fudan University, Shanghai, China. 13. Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain. 14. CIBER Enfermedades Respiratorias, Madrid, Spain. 15. Servicio de Microbiología Clínica y Enfermedades Infecciosas, Hospital General Universitario Gregorio Marañón, Madrid, Spain. 16. Barcelona Institute for Global Health, Barcelona, Spain. 17. Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique. 18. Ifakara Health Institute, Bagamoyo, Tanzania. 19. School of Medicine, University of California, San Francisco, USA. 20. Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea. 21. Department of Microbiology, Mahidol University, Bangkok, Thailand. 22. National Science and Technology Development Agency, Bangkok, Thailand. 23. Institut Pasteur de Madagascar, Antananarivo, Madagascar. 24. Department of Medicine, Swiss Tropical and Public Health Institute, Basel, Switzerland. 25. Université Paris-Saclay, Paris, France. 26. INSERM-Université de Paris, Paris, France. 27. Laboratório de Biologia Molecular Aplicada a Micobactérias, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. 28. Centro de Ciências Biológicas e da Saúde, Universidade do Estado do Pará, Belém, Brazil. 29. Instituto Evandro Chagas, Ananindeua, Brazil. 30. Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana. 31. Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
Abstract
Background: Lineage 1 (L1) and 3 (L3) are two lineages of the Mycobacterium tuberculosis complex (MTBC) causing tuberculosis (TB) in humans. L1 and L3 are prevalent around the rim of the Indian Ocean, the region that accounts for most of the world's new TB cases. Despite their relevance for this region, L1 and L3 remain understudied. Methods: We analyzed 2,938 L1 and 2,030 L3 whole genome sequences originating from 69 countries. We reconstructed the evolutionary history of these two lineages and identified genes under positive selection. Results: We found a strongly asymmetric pattern of migration from South Asia toward neighboring regions, highlighting the historical role of South Asia in the dispersion of L1 and L3. Moreover, we found that several genes were under positive selection, including genes involved in virulence and resistance to antibiotics. For L1 we identified signatures of local adaptation at the esxH locus, a gene coding for a secreted effector that targets the human endosomal sorting complex, and is included in several vaccine candidates. Conclusions: Our study highlights the importance of genetic diversity in the MTBC, and sheds new light on two of the most important MTBC lineages affecting humans. Copyright:
Background: Lineage 1 (L1) and 3 (L3) are two lineages of the Mycobacterium tuberculosis complex (MTBC) causing tuberculosis (TB) in humans. L1 and L3 are prevalent around the rim of the Indian Ocean, the region that accounts for most of the world's new TB cases. Despite their relevance for this region, L1 and L3 remain understudied. Methods: We analyzed 2,938 L1 and 2,030 L3 whole genome sequences originating from 69 countries. We reconstructed the evolutionary history of these two lineages and identified genes under positive selection. Results: We found a strongly asymmetric pattern of migration from South Asia toward neighboring regions, highlighting the historical role of South Asia in the dispersion of L1 and L3. Moreover, we found that several genes were under positive selection, including genes involved in virulence and resistance to antibiotics. For L1 we identified signatures of local adaptation at the esxH locus, a gene coding for a secreted effector that targets the human endosomal sorting complex, and is included in several vaccine candidates. Conclusions: Our study highlights the importance of genetic diversity in the MTBC, and sheds new light on two of the most important MTBC lineages affecting humans. Copyright:
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