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LOCAL ADAPTATION IN POPULATIONS OF MYCOBACTERIUM TUBERCULOSIS ENDEMIC TO THE INDIAN OCEAN RIM [VERSION 2; PEER REVIEW: 3 APPROVED]
Author
Menardo, Fabrizio
Rutaihwa, Liliana K.
Zwyer, Michaela
Borrell, Sonia
Comas, Iñaki
Conceição, Emilyn Costa
Coscolla, Mireia
Cox, Helen
Joloba, Moses
Yunn Dou, Horng
Feldmann, Julia
Fenner, Lukas
Fyfe, Janet
Gao, Qian
Viedma, Darío García de
Garcia-Basteiro, Alberto L.
Gygli, Sebastian M.
Hella, Jerry
Hiza, Hellen
Jugheli, Levan
Kamwela, Lujeko
Kato-Maeda, Midori
Liu, Qingyun
Ley, Serej D.
Loiseau, Chloe
Mahasirimongkol, Surakameth
Malla, Bijaya
Palittapongarnpim, Prasit
Rakotosamimanana, Niaina
Rasolofo, Voahangy
Reinhard, Miriam
Reither, Klaus
Sasamalo, Mohamed
Duarte, Rafael Silva
Sola, Christophe
Suffys, Philip
Lima, Karla Valeria Batista
Yeboah-Manu, Dorothy
Beisel, Christian
Brites, Daniela
Gagneux, Sebastien
Rutaihwa, Liliana K.
Zwyer, Michaela
Borrell, Sonia
Comas, Iñaki
Conceição, Emilyn Costa
Coscolla, Mireia
Cox, Helen
Joloba, Moses
Yunn Dou, Horng
Feldmann, Julia
Fenner, Lukas
Fyfe, Janet
Gao, Qian
Viedma, Darío García de
Garcia-Basteiro, Alberto L.
Gygli, Sebastian M.
Hella, Jerry
Hiza, Hellen
Jugheli, Levan
Kamwela, Lujeko
Kato-Maeda, Midori
Liu, Qingyun
Ley, Serej D.
Loiseau, Chloe
Mahasirimongkol, Surakameth
Malla, Bijaya
Palittapongarnpim, Prasit
Rakotosamimanana, Niaina
Rasolofo, Voahangy
Reinhard, Miriam
Reither, Klaus
Sasamalo, Mohamed
Duarte, Rafael Silva
Sola, Christophe
Suffys, Philip
Lima, Karla Valeria Batista
Yeboah-Manu, Dorothy
Beisel, Christian
Brites, Daniela
Gagneux, Sebastien
Affilliation
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
Institute of Biomedicine of Valencia. Valencia, Spain.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
I2SysBio. University of Valencia. Valencia, Spain.
Institute of Infectious Diseases and Molecular Medicine, University of Cape Town. Cape Town, South Africa.
Department of Medical Microbiology, Makerere University. Kampala, Uganda.
National Institute of Infectious Diseases and Vaccinology, National Health Research Institute. Zhunan, Taiwan.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland / Institute for Social and Preventive Medicine, University of Bern. Bern, Switzerland.
Victorian Infectious Diseases Reference Laboratory. Melbourne, Australia.
Institute of Medical Microbiology, School of Basic Medical Science of Fudan University. Shanghai, China.
Instituto de Investigación Sanitaria Gregorio Marañón. Madrid, Spain / Servicio de Microbiología Clínica y Enfermedades Infecciosas, Hospital General Universitario Gregorio Marañón. Madrid, Spain.
Barcelona Institute for Global Health. Barcelona, Spain / Centro de Investigação em Saúde de Manhiça. Maputo, Mozambique.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland / Ifakara Health Institute. Bagamoyo, Tanzania.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland / Ifakara Health Institute, Bagamoyo, Tanzania.
School of Medicine, University of California. San Francisco, USA.
Institute of Medical Microbiology, School of Basic Medical Science of Fudan University. Shanghai, China.
Institute of Medical Microbiology, School of Basic Medical Science of Fudan University. Shanghai, China.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland / Papua New Guinea Institute of Medical Research, Goroka. Papua New Guinea.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
Department of Microbiology, Mahidol University. Bangkok, Thailand / National Science and Technology Development Agency. Bangkok, Thailand.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
Department of Microbiology, Mahidol University. Bangkok, Thailand / National Science and Technology Development Agency. Bangkok, Thailand.
Institut Pasteur de Madagascar. Antananarivo, Madagascar.
Institut Pasteur de Madagascar. Antananarivo, Madagascar.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
University of Basel, Basel, Switzerland / Department of Medicine, Swiss Tropical and Public Health Institute. Basel, Switzerland.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland / Ifakara Health Institute. Bagamoyo, Tanzania.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Rio de Janeiro, RJ, Brasil.
Université Paris-Saclay. Paris, France / INSERM-Université de Paris. Paris, France.
Fundação Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil.
Universidade do Estado do Pará. Centro de Ciências Biológicas e da Saúde. Belém, PA, Brasil / Instituto Evandro Chagas. Ananindeua, PA, Brasil.
Noguchi Memorial Institute for Medical Research. University of Ghana, Accra, Ghana.
Department of Biosystems Science and Engineering, ETH Zürich. Basel, Switzerland.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
Institute of Biomedicine of Valencia. Valencia, Spain.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
I2SysBio. University of Valencia. Valencia, Spain.
Institute of Infectious Diseases and Molecular Medicine, University of Cape Town. Cape Town, South Africa.
Department of Medical Microbiology, Makerere University. Kampala, Uganda.
National Institute of Infectious Diseases and Vaccinology, National Health Research Institute. Zhunan, Taiwan.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland / Institute for Social and Preventive Medicine, University of Bern. Bern, Switzerland.
Victorian Infectious Diseases Reference Laboratory. Melbourne, Australia.
Institute of Medical Microbiology, School of Basic Medical Science of Fudan University. Shanghai, China.
Instituto de Investigación Sanitaria Gregorio Marañón. Madrid, Spain / Servicio de Microbiología Clínica y Enfermedades Infecciosas, Hospital General Universitario Gregorio Marañón. Madrid, Spain.
Barcelona Institute for Global Health. Barcelona, Spain / Centro de Investigação em Saúde de Manhiça. Maputo, Mozambique.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland / Ifakara Health Institute. Bagamoyo, Tanzania.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland / Ifakara Health Institute, Bagamoyo, Tanzania.
School of Medicine, University of California. San Francisco, USA.
Institute of Medical Microbiology, School of Basic Medical Science of Fudan University. Shanghai, China.
Institute of Medical Microbiology, School of Basic Medical Science of Fudan University. Shanghai, China.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland / Papua New Guinea Institute of Medical Research, Goroka. Papua New Guinea.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
Department of Microbiology, Mahidol University. Bangkok, Thailand / National Science and Technology Development Agency. Bangkok, Thailand.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
Department of Microbiology, Mahidol University. Bangkok, Thailand / National Science and Technology Development Agency. Bangkok, Thailand.
Institut Pasteur de Madagascar. Antananarivo, Madagascar.
Institut Pasteur de Madagascar. Antananarivo, Madagascar.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
University of Basel, Basel, Switzerland / Department of Medicine, Swiss Tropical and Public Health Institute. Basel, Switzerland.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland / Ifakara Health Institute. Bagamoyo, Tanzania.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Rio de Janeiro, RJ, Brasil.
Université Paris-Saclay. Paris, France / INSERM-Université de Paris. Paris, France.
Fundação Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil.
Universidade do Estado do Pará. Centro de Ciências Biológicas e da Saúde. Belém, PA, Brasil / Instituto Evandro Chagas. Ananindeua, PA, Brasil.
Noguchi Memorial Institute for Medical Research. University of Ghana, Accra, Ghana.
Department of Biosystems Science and Engineering, ETH Zürich. Basel, Switzerland.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland / University of Basel, Basel, Switzerland.
Abstract
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.
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