title: Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages.
abstract: Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration.
authors: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Switzerland.
authors: David
authors: D
authors: Stucki
authors: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Switzerland.
authors: Daniela
authors: D
authors: Brites
authors: Forschungszentrum Borstel, Germany.|Institut Pasteur de Tunis, Université de Tunis El Manar, Tunis, Tunisia.
authors: Leïla
authors: L
authors: Jeljeli
authors: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Switzerland.
authors: Mireia
authors: M
authors: Coscolla
authors: The Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institutes of Biomedical Sciences and Institute of Medical Microbiology, School of Basic Medical Science of Fudan University, Shanghai, China.
authors: Qingyun
authors: Q
authors: Liu
authors: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Switzerland.
authors: Andrej
authors: A
authors: Trauner
authors: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Switzerland.|Institute for Social and Preventive Medicine, University of Bern, Switzerland.
authors: Lukas
authors: L
authors: Fenner
authors: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Switzerland.
authors: Liliana
authors: L
authors: Rutaihwa
authors: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Switzerland.
authors: Sonia
authors: S
authors: Borrell
authors: Laboratory of Infection and Immunity, School of Basic Medical Science, West China Center of Medical Sciences, Sichuan University, Chengdu, Sichuan 610041, China.
authors: Tao
authors: T
authors: Luo
authors: The Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institutes of Biomedical Sciences and Institute of Medical Microbiology, School of Basic Medical Science of Fudan University, Shanghai, China.
authors: Qian
authors: Q
authors: Gao
authors: School of Medicine, University of California, San Francisco, USA.
authors: Midori
authors: M
authors: Kato-Maeda
authors: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Switzerland.|Institute for Social and Preventive Medicine, University of Bern, Switzerland.
authors: Marie
authors: M
authors: Ballif
authors: Institute for Social and Preventive Medicine, University of Bern, Switzerland.
authors: Matthias
authors: M
authors: Egger
authors: Laboratòrio de Saùde Publica, Lisbon, Portugal.
authors: Rita
authors: R
authors: Macedo
authors: Institut Pasteur de Tunis, Université de Tunis El Manar, Tunis, Tunisia.
authors: Helmi
authors: H
authors: Mardassi
authors: Hospital Nossa Senhora Da Paz, Cubal, Benguela, Angola.
authors: Milagros
authors: M
authors: Moreno
authors: Servei de Microbiologia, Hospital Clínic-ISGlobal, Barcelona, Spain.
authors: Griselda
authors: G
authors: Tudo Vilanova
authors: Victorian Infectious Diseases Reference Laboratory, Victoria, Australia.
authors: Janet
authors: J
authors: Fyfe
authors: Victorian Infectious Diseases Reference Laboratory, Victoria, Australia.
authors: Maria
authors: M
authors: Globan
authors: Ifakara Health Institute, Bagamoyo, Tanzania.
authors: Jackson
authors: J
authors: Thomas
authors: Public Health Ontario, Toronto, Canada.
authors: Frances
authors: F
authors: Jamieson
authors: Public Health Ontario, Toronto, Canada.
authors: Jennifer L
authors: JL
authors: Guthrie
authors: Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana.
authors: Adwoa
authors: A
authors: Asante-Poku
authors: Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana.
authors: Dorothy
authors: D
authors: Yeboah-Manu
authors: Department of Medical Microbiology, Makerere University, Kampala, Uganda.
authors: Eddie
authors: E
authors: Wampande
authors: Department of Medical Microbiology, Makerere University, Kampala, Uganda.|Department of Global Health, University of Amsterdam, Amsterdam, the Netherlands.
authors: Willy
authors: W
authors: Ssengooba
authors: Department of Medical Microbiology, Makerere University, Kampala, Uganda.
authors: Moses
authors: M
authors: Joloba
authors: Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, USA.
authors: W
authors: W
authors: Henry Boom
authors: LabPlus, Auckland City Hospital, Auckland, New Zealand.
authors: Indira
authors: I
authors: Basu
authors: LabPlus, Auckland City Hospital, Auckland, New Zealand.
authors: James
authors: J
authors: Bower
authors: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors: Margarida
authors: M
authors: Saraiva
authors: Oswaldo Cruz Institute, Brazil.
authors: Sidra E G
authors: SEG
authors: Vaconcellos
authors: Oswaldo Cruz Institute, Brazil.
authors: Philip
authors: P
authors: Suffys
authors: Institute of Infectious Disease and Molecular Medicine and Department of Clinical Laboratory Sciences, University of Cape Town, South Africa.
authors: Anastasia
authors: A
authors: Koch
authors: Institute of Infectious Disease and Molecular Medicine and Department of Clinical Laboratory Sciences, University of Cape Town, South Africa.|Department of Medicine, Imperial College London, UK.|The Francis Crick Institute Mill Hill Laboratory, London, UK.
authors: Robert
authors: R
authors: Wilkinson
authors: Institute of Infectious Disease and Molecular Medicine and Department of Clinical Laboratory Sciences, University of Cape Town, South Africa.
authors: Linda
authors: L
authors: Gail-Bekker
authors: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Switzerland.
authors: Bijaya
authors: B
authors: Malla
authors: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Switzerland.|Papua New Guinea Institute of Medical Research, Goroka, PNG.
authors: Serej D
authors: SD
authors: Ley
authors: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Switzerland.
authors: Hans-Peter
authors: HP
authors: Beck
authors: Insitute of Tropical Medicine, Antwerp, Belgium.
authors: Bouke C
authors: BC
authors: de Jong
authors: Tartu University Hospital United Laboratories, Mycobacteriology, Tartu, Estonia.
authors: Kadri
authors: K
authors: Toit
authors: Clinical Research Department, Epicentre, Paris, France.
authors: Elisabeth
authors: E
authors: Sanchez-Padilla
authors: Clinical Research Department, Epicentre, Paris, France.
authors: Maryline
authors: M
authors: Bonnet
authors: Department of Microbiology, University Hospital La Fe, Valencia, Spain.
authors: Ana
authors: A
authors: Gil-Brusola
authors: Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.
authors: Matthias
authors: M
authors: Frank
authors: Institute Laboratory for Tuberculosis Research (LTR), Biotechnology Center (BTC), University of Yaoundé I, Yaoundé, Cameroon.
authors: Veronique N
authors: VN
authors: Penlap Beng
authors: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors: Kathleen
authors: K
authors: Eisenach
authors: Department of Medical Laboratory Technology, Faculty of Medical Technology, Baghdad, Iraq.
authors: Issam
authors: I
authors: Alani
authors: Institute of Tropical Medicine and Infectious Diseases (ITROMID), Jomo Kenyatta University of Agriculture and Technology (JKUAT), Nairobi, Kenya.
authors: Perpetual
authors: P
authors: Wangui Ndung'u
authors: Department of Pathology, Aga Khan University Hospital (AKUH), Nairobi, Kenya.
authors: Gunturu
authors: G
authors: Revathi
authors: Insitute of Tropical Medicine, Antwerp, Belgium.|Medical Research Council, Fajara, the Gambia.
authors: Florian
authors: F
authors: Gehre
authors: Insitute of Tropical Medicine, Antwerp, Belgium.
authors: Suriya
authors: S
authors: Akter
authors: Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.|Fondation Congolaise pour la Recherche Médicale, Université Marien Gouabi, Brazzaville, Congo.
authors: Francine
authors: F
authors: Ntoumi
authors: Right to Care and the Clinical HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
authors: Lynsey
authors: L
authors: Stewart-Isherwood
authors: National Institute of Medical Research, Mbeya Medical Research Centre (NIMR-MMRC), Mbeya, Tanzania.
authors: Nyanda E
authors: NE
authors: Ntinginya
authors: Division of Infectious Diseases and Tropical Medicine, Medical Centre of the University of Munich, Munich, Germany; German Centre for Infection Research (DZIF), partner site Munich, Germany.
authors: Andrea
authors: A
authors: Rachow
authors: Division of Infectious Diseases and Tropical Medicine, Medical Centre of the University of Munich, Munich, Germany; German Centre for Infection Research (DZIF), partner site Munich, Germany.
authors: Michael
authors: M
authors: Hoelscher
authors: Emerging Bacterial Pathogens Unit, IRCCS, San Raffaele Scientific Institute, Milan, Italy.
authors: Daniela Maria
authors: DM
authors: Cirillo
authors: Riga East University Hospital, Centre of Tuberculosis and Lung Diseases, Riga, Latvia.
authors: Girts
authors: G
authors: Skenders
authors: WHO Supranational TB Reference Laboratory, Department of Microbiology, The Public Health Agency of Sweden, Solna, Sweden.
authors: Sven
authors: S
authors: Hoffner
authors: Department of Immunology and Cell Biology, Institute of Biotechnology, Vilnius University, Vilnius, Lithuania.
authors: Daiva
authors: D
authors: Bakonyte
authors: Department of Immunology and Cell Biology, Institute of Biotechnology, Vilnius University, Vilnius, Lithuania.
authors: Petras
authors: P
authors: Stakenas
authors: Institute for Epidemiology, Schleswig-Holstein University Hospital, Kiel, Germany.
authors: Roland
authors: R
authors: Diel
authors: National Tuberculosis Reference Laboratory, Phthysiopneumology Institute, Chisinau, Republic of Moldova.
authors: Valeriu
authors: V
authors: Crudu
authors: 'Marius Nasta' Pneumophtisiology Institute, Bucharest, Romania.
authors: Olga
authors: O
authors: Moldovan
authors: Department of Infection and Immunity, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Sahal
authors: S
authors: Al-Hajoj
authors: Instituto de Medicina Tropical Alexander von Humboldt, Molecular Epidemiology Unit-Tuberculosis, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors: Larissa
authors: L
authors: Otero
authors: Instituto de Medicina Tropical Alexander von Humboldt, Molecular Epidemiology Unit-Tuberculosis, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors: Francesca
authors: F
authors: Barletta
authors: Alpert School of Medicine at Brown University, Providence, Rhode Island, USA.|Moi University School of Medicine, Eldoret, Kenya.
authors: E
authors: E
authors: Jane Carter
authors: Moi University School of Medicine, Eldoret, Kenya.
authors: Lameck
authors: L
authors: Diero
authors: Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, F-59000 Lille, France.
authors: Philip
authors: P
authors: Supply
authors: Institute of Biomedicine of Valencia (IBV-CSIC), 46010, Valencia, Spain.|CIBER Epidemiology and Public Health, Madrid, Spain.
authors: Iñaki
authors: I
authors: Comas
authors: Forschungszentrum Borstel, Germany.|German Center for Infection Research, Borstel Site, Borstel, Germany.
authors: Stefan
authors: S
authors: Niemann
authors: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Switzerland.
authors: Sebastien
authors: S
authors: Gagneux
mesh_terms: D004269:DNA, Bacterial / Q000032:analysis*; D023281:Genomics / Q000379:methods*; D005838:Genotype; D014943:Global Health; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D058974:Phylogeography; D011110:Polymorphism, Genetic / Q000235:genetics*; D014376:Tuberculosis / Q000235:genetics / Q000382:microbiology*
chemical_list: D004269:DNA, Bacterial