Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium

Lung infections with $\textit{Mycobacterium abscessus}$, a species of multidrug-resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF), in whom $\textit{M. abscessus}$ accelerates inflammatory lung damage, leading to increased morbidity and mortality. Previously, $\textit{M. abscessus}$ was thought to be independently acquired by susceptible individuals from the environment. However, using whole-genome analysis of a global collection of clinical isolates, we show that the majority of $\textit{M. abscessus}$ infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge.Wellcome Trust (Grant IDs: 098051, 107032AIA), Medical Research Council, UK Cystic Fibrosis Trust, Papworth Hospital, National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, NIHR Specialist Respiratory Biomedical Research Unit, Imperial College London, The UK Clinical Research Collaboration Translational Infection Research Initiative, CF Foundation Therapeutics grant, Australian National Health and Medical Research Council, The Prince Charles Hospital Foundation, National Services Division NHS Scotlan