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

Josephine M Bryant, Dorothy M Grogono, Daniela Rodriguez-Rincon, Isobel Everall, Karen P Brown, Pablo Moreno, Deepshikha Verma, Emily Hill, Judith Drijkoningen, Peter Gilligan, Charles R Esther, Peadar G Noone, Olivia Giddings, Scott C Bell, Rachel Thomson, Claire E Wainwright, Chris Coulter, Sushil Pandey, Michelle E Wood, Rebecca E Stockwell, Kay A Ramsay, Laura J Sherrard, Timothy J Kidd, Nassib Jabbour, Graham R Johnson, Luke D Knibbs, Lidia Morawska, Peter D Sly, Andrew Jones, Diana Bilton, Ian Laurenson, Michael Ruddy, Stephen Bourke, Ian Cjw Bowler, Stephen J Chapman, Andrew Clayton, Mairi Cullen, Thomas Daniels, Owen Dempsey, Miles Denton, Maya Desai, Richard J Drew, Frank Edenborough, Jason Evans, Jonathan Folb, Helen Humphrey, Barbara Isalska, Søren Jensen-Fangel, Bodil Jönsson, Andrew M Jones, Terese L Katzenstein, Troels Lillebaek, Gordon MacGregor, Sarah Mayell, Michael Millar, Deborah Modha, Edward F Nash, Christopher O'Brien, Deirdre O'Brien, Chandra Ohri, Caroline S Pao, Daniel Peckham, Felicity Perrin, Audrey Perry, Tania Pressler, Laura Prtak, Tavs Qvist, Ali Robb, Helen Rodgers, Kirsten Schaffer, Nadia Shafi, Jakko van Ingen, Martin Walshaw, Danie Watson, Noreen West, Joanna Whitehouse, Charles S Haworth, Simon R Harris, Diane Ordway, Julian Parkhill, R Andres Floto

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.