Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany; German Center for Infection Research, Partner site Hamburg-Lübeck-Borstel-Riems, Germany
Maxime Barbier
Laboratoire Biologie Intégrative des Populations, Evolution Moléculaire, Ecole Pratique des Hautes Etudes, PSL University, Paris, France; Institut de Systématique, Evolution, Biodiversité, UMR-CNRS 7205, Muséum National d’Histoire Naturelle, Université Pierre et Marie Curie, Ecole Pratique des Hautes Etudes, Sorbonne Universités, Paris, France
Helen Cox
Division of Medical Microbiology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
Laboratoire Biologie Intégrative des Populations, Evolution Moléculaire, Ecole Pratique des Hautes Etudes, PSL University, Paris, France; Institut de Systématique, Evolution, Biodiversité, UMR-CNRS 7205, Muséum National d’Histoire Naturelle, Université Pierre et Marie Curie, Ecole Pratique des Hautes Etudes, Sorbonne Universités, Paris, France; CIRI INSERM U1111, University of Lyon, Lyon, France
Silke Feuerriegel
Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany; German Center for Infection Research, Partner site Hamburg-Lübeck-Borstel-Riems, Germany
Thomas Andreas Kohl
Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany; German Center for Infection Research, Partner site Hamburg-Lübeck-Borstel-Riems, Germany
Roland Diel
Institute for Epidemiology, Schleswig-Holstein University Hospital, Kiel, Germany
Sonia Borrell
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland
Sebastien Gagneux
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland
Imperial College London, London, United Kingdom; Public Health England, London, United Kingdom
Sönke Andres
Division of Mycobacteriology, National Tuberculosis Reference Laboratory, Research Center Borstel, Borstel, Germany
Ulrich Nübel
Microbial Genome Research, Leibniz-Institut DSMZ- Deutsche Sammlung von Mikroorganismen und Zellkulturen, Braunschweig, Germany; German Center for Infection Research, Braunschweig, Germany
Philip Supply
Université de Lille, CNRS UMR 8204, Inserm U1019, CHU de Lille, Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, Lille, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche, Center for Infection and Immunity of Lille, Lille, France; Center for Infection and Immunity of Lille, Université de Lille Nord de France, Lille, France; Center for Infection and Immunity of Lille, Institut Pasteur de Lille, Lille, France
Thierry Wirth
Laboratoire Biologie Intégrative des Populations, Evolution Moléculaire, Ecole Pratique des Hautes Etudes, PSL University, Paris, France; Institut de Systématique, Evolution, Biodiversité, UMR-CNRS 7205, Muséum National d’Histoire Naturelle, Université Pierre et Marie Curie, Ecole Pratique des Hautes Etudes, Sorbonne Universités, Paris, France
Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany; German Center for Infection Research, Partner site Hamburg-Lübeck-Borstel-Riems, Germany
Bacterial factors favoring the unprecedented multidrug-resistant tuberculosis (MDR-TB) epidemic in the former Soviet Union remain unclear. We utilized whole genome sequencing and Bayesian statistics to analyze the evolutionary history, temporal emergence of resistance and transmission networks of MDR Mycobacterium tuberculosis complex isolates from Karakalpakstan, Uzbekistan (2001–2006). One clade (termed Central Asian outbreak, CAO) dating back to 1974 (95% HPD 1969–1982) subsequently acquired resistance mediating mutations to eight anti-TB drugs. Introduction of standardized WHO-endorsed directly observed treatment, short-course in Karakalpakstan in 1998 likely selected for CAO-strains, comprising 75% of sampled MDR-TB isolates in 2005/2006. CAO-isolates were also identified in a published cohort from Russia (2008–2010). Similarly, the presence of mutations supposed to compensate bacterial fitness deficits was associated with transmission success and higher drug resistance rates. The genetic make-up of these MDR-strains threatens the success of both empirical and standardized MDR-TB therapies, including the newly WHO-endorsed short MDR-TB regimen in Uzbekistan.
