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Sci Adv. 2018 Oct 17;4(10):eaat5869. doi: 10.1126/sciadv.aat5869. eCollection 2018 Oct.

Global expansion of Mycobacterium tuberculosis lineage 4 shaped by colonial migration and local adaptation.

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Division of Infectious Diseases and Environmental Health, Norwegian Institute of Public Health, Lovisenberggata 8, 0456 Oslo, Norway.
Division of Infectious Disease, Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53726, USA.
Department of Medical Microbiology and Immunology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53726, USA.
Laboratory of Molecular Biology Applied to Mycobacteria, Oswaldo Cruz Institute, Avenida Brasil 4365, C.P. 926, Manguinhos 21040-360, Rio de Janeiro, Brazil.
Department of Paediatric Infectious Diseases, Imperial College London, W2 1NY, London, UK.
Instituto Nacional de Enfermedades Infecciosas, ANLIS Carlos Malbran, Buenos Aires, Argentina.
Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Buenos Aires, Argentina.
Department of Medical Biochemistry and Microbiology, Zoonosis Science Center, Uppsala University, Uppsala, Sweden.
Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Life and Environmental Sciences and Sydney Medical School, The University of Sydney, Sydney, New South Wales 2006, Australia.
Public Health Agency of Sweden, Nobels vg 18, SE-171 82 Solna, Sweden.
Laboratorio de Bacteriologia da Tuberculose, Centro de Referłncia Professor Helio Fraga-Jacarepagu, Estrada de Curicica 2000, Brazil.
Instituto de Investigao do Medicamento, Faculdade de Farmcia, Universidade de Lisboa, Lisboa, Portugal.
Unidade de Microbiologia Medica, Global Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal.
Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
Liverpool School of Tropical medicine, Department of Clinical Sciences, Liverpool, UK.
Birat-Nepal Medical Trust, Lazimpat, Kathmandu, Nepal.
Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
Pham Ngoc Thach Hospital for TB and Lung Diseases, Ho Chi Minh City, Vietnam.
Department of Anthropology, University of Iowa, Iowa City, IA 52242, USA.
Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.
Center for Infectious Disease Research, Diagnostics and Perinatal Screening, National Institute for Public Health and the Environment, P.O. Box 1, 3720 BA Bilthoven, Netherlands.
Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA.
Department of Biochemistry and Molecular Biology and Bio21 Institute, University of Melbourne, Melbourne, Victoria, Australia.
Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
Mailman School of Public Health, Columbia University, 722 West 168th Street, New York, NY 10032, USA.
UCL Genetics Institute, University College London, London WC1E 6BT, UK.


On the basis of population genomic and phylogeographic analyses of 1669 Mycobacterium tuberculosis lineage 4 (L4) genomes, we find that dispersal of L4 has been completely dominated by historical migrations out of Europe. We demonstrate an intimate temporal relationship between European colonial expansion into Africa and the Americas and the spread of L4 tuberculosis (TB). Markedly, in the age of antibiotics, mutations conferring antimicrobial resistance overwhelmingly emerged locally (at the level of nations), with minimal cross-border transmission of resistance. The latter finding was found to reflect the relatively recent emergence of these mutations, as a similar degree of local restriction was observed for susceptible variants emerging on comparable time scales. The restricted international transmission of drug-resistant TB suggests that containment efforts at the level of individual countries could be successful.

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