Lung infections with Mycobacterium abscessus, a species of multidrug-resistant
nontuberculous mycobacteria, are emerging as an important global threat to individuals with
cystic fibrosis (CF), in whom M. abscessus accelerates inflammatory lung damage, leading to
increased morbidity and mortality. Previously, 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 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.