Species belonging to the Mycobacterium kansasii complex (MKC) are frequently isolated from humans and the environment and can cause serious diseases. The most common MKC infections are caused by the species M. kansasii (sensu stricto), leading to tuberculosis-like disease. However, a broad spectrum of virulence, antimicrobial resistance and pathogenicity of these non-tuberculous mycobacteria (NTM) are observed across the MKC. Many genomic aspects of the MKC that relate to these broad phenotypes are not well elucidated. Here, we performed genomic analyses from a collection of 665 MKC strains, isolated from environmental, animal and human sources. We inferred the MKC pangenome, mobilome, resistome, virulome and defence systems and show that the MKC species harbours unique and shared genomic signatures. High frequency of presence of prophages and different types of defence systems were observed. We found that the M. kansasii species splits into four lineages, of which three are lowly represented and mainly in Brazil, while one lineage is dominant and globally spread. Moreover, we show that four sub-lineages of this most distributed M. kansasii lineage emerged during the twentieth century. Further analysis of the M. kansasii genomes revealed almost 300 regions of difference contributing to genomic diversity, as well as fixed mutations that may explain the M. kansasii's increased virulence and drug resistance.

Department of Biosciences Nottingham Trent University Nottingham UK

Department of Diagnostic Mycobacterioses Regional Institute of Public Health Ostrava Czech Republic

Department of Microbiological Pathology Sefako Makgatho Health Sciences University Pretoria South Africa

German Center for Infection Research Partner Site Hamburg Lübeck Borstel Riems Borstel Germany

Global Institute of Health University of Antwerp Antwerp Belgium

Laboratório de Bacteriologia e Bioensaios Instituto Nacional de Infectologia Fiocruz Rio de Janeiro RJ Brazil

Laboratório de Biologia do Reconhecer Universidade Estadual do Norte Fluminense Darcy Ribeiro Campos dos Goytacazes RJ Brazil

Laboratório de Biologia Molecular Aplicada a Micobactérias Instituto Oswaldo Cruz Fiocruz Rio de Janeiro RJ Brazil

Laboratório de Genética Molecular de Microrganismos Instituto Oswaldo Cruz Fiocruz Rio de Janeiro RJ Brazil

Laboratório de Referência Nacional para Tuberculose Centro de Referência Professor Hélio Fraga Escola Nacional de Saúde Pública Fiocruz Rio de Janeiro RJ Brazil

Laboratory of Molecular Epidemiology and Evolutionary Genetics St Petersburg Pasteur Institute St Petersburg Russia

Molecular and Experimental Mycobacteriology Research Center Borstel Borstel Germany

Mycobacteria Reference Laboratory Croatian National Institute of Public Health Zagreb Croatia

Mycobacteriology Section of Microbiology Laboratory North Estonia Medical Centre Tallinn Estonia

National Health Laboratory Service Dr George Mukhari Tertiary Laboratory Medical Microbiology Pretoria South Africa

National Institute for Public Health and the Environment Bilthoven Netherlands

National Reference Laboratory for Mycobacteria University Clinic of Respiratory and Allergic Diseases Golnik Slovenia

Núcleo de Doenças Infecciosas Universidade Federal do Espírito Santo Vitória ES Brazil

One Health Research Group Universidad de Las Américas Quito Ecuador

Serviço de Pesquisa Clínica Centro de Referência Professor Hélio Fraga Escola Nacional de Saúde Pública Fiocruz Rio de Janeiro RJ Brazil

St Petersburg Research Institute of Phthisiopulmonology St Petersburg Russia

TB and Mycobacteria Unit Institut Pasteur de Guadeloupe Guadeloupe France

Tuberculosis Department Servicio Autónomo Instituto de Biomedicina Dr Jacinto Convit Universidad Central de Venezuela Caracas Venezuela

Unit of Mycobacteriology Institute of Tropical Medicine Antwerp Belgium

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