title: Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium.
abstract: 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.
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.|University of Cambridge Department of Medicine, MRC-Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Bryant
authors.affiliation: University of Cambridge Department of Medicine, MRC-Laboratory of Molecular Biology, Cambridge, UK.|Cambridge Centre for Lung Infection, Papworth Hospital, Cambridge, UK.
authors.forename: Dorothy M
authors.initials: DM
authors.lastname: Grogono
authors.affiliation: University of Cambridge Department of Medicine, MRC-Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Daniela
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authors.lastname: Rodriguez-Rincon
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Isobel
authors.initials: I
authors.lastname: Everall
authors.affiliation: University of Cambridge Department of Medicine, MRC-Laboratory of Molecular Biology, Cambridge, UK.|Cambridge Centre for Lung Infection, Papworth Hospital, Cambridge, UK.
authors.forename: Karen P
authors.initials: KP
authors.lastname: Brown
authors.affiliation: EMBL European Bioinformatics Institute, Hinxton, UK.
authors.forename: Pablo
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authors.lastname: Moreno
authors.affiliation: Mycobacteria Research Laboratory, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins CO, USA.
authors.forename: Deepshikha
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authors.lastname: Verma
authors.affiliation: Mycobacteria Research Laboratory, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins CO, USA.
authors.forename: Emily
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authors.lastname: Hill
authors.affiliation: University of Cambridge Department of Medicine, MRC-Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Judith
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authors.lastname: Drijkoningen
authors.affiliation: University of North Carolina School of Medicine, NC, USA.
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authors.lastname: Gilligan
authors.affiliation: University of North Carolina School of Medicine, NC, USA.
authors.forename: Charles R
authors.initials: CR
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authors.affiliation: University of North Carolina School of Medicine, NC, USA.
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authors.affiliation: University of North Carolina School of Medicine, NC, USA.
authors.forename: Olivia
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authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia.|School of Medicine, The University of Queensland, Australia.|The Prince Charles Hospital, Brisbane, Australia.
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authors.initials: SC
authors.lastname: Bell
authors.affiliation: Gallipoli Medical Research Centre, University of Queensland, Brisbane, Australia.
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authors.affiliation: School of Medicine, The University of Queensland, Australia.|Lady Cilento Children's Hospital, Brisbane.
authors.forename: Claire E
authors.initials: CE
authors.lastname: Wainwright
authors.affiliation: Queensland Mycobacterial Reference Laboratory, Brisbane, Australia.
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authors.lastname: Coulter
authors.affiliation: Queensland Mycobacterial Reference Laboratory, Brisbane, Australia.
authors.forename: Sushil
authors.initials: S
authors.lastname: Pandey
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia.|School of Medicine, The University of Queensland, Australia.|The Prince Charles Hospital, Brisbane, Australia.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Wood
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia.|School of Medicine, The University of Queensland, Australia.
authors.forename: Rebecca E
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authors.lastname: Stockwell
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia.|School of Medicine, The University of Queensland, Australia.
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authors.initials: KA
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authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: Laura J
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authors.affiliation: Centre for Experimental Medicine, Queen's University Belfast, UK.|School of Chemistry and Biomolecular sciences, The University of Queensland, Australia.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Kidd
authors.affiliation: Queensland University of Technology, Brisbane, Australia.|International Laboratory for Air Quality and Health, Queensland University of Technology, Brisbane, Australia.
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authors.lastname: Jabbour
authors.affiliation: International Laboratory for Air Quality and Health, Queensland University of Technology, Brisbane, Australia.
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authors.initials: GR
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authors.affiliation: School of Public Health, The University of Queensland, Brisbane, Australia.
authors.forename: Luke D
authors.initials: LD
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authors.affiliation: International Laboratory for Air Quality and Health, Queensland University of Technology, Brisbane, Australia.
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authors.affiliation: Child Health Research Centre, The University of Queensland, Brisbane, Australia.
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authors.affiliation: Royal Brompton and Harefield NHS Foundation Trust, UK.
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authors.affiliation: Scottish Mycobacteria Reference Laboratory, UK.
authors.forename: Ian
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authors.affiliation: Wales Centre for Mycobacteria, UK.
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authors.affiliation: The Newcastle upon Tyne Hospitals NHS Foundation Trust, UK.
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authors.initials: S
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authors.affiliation: Oxford University Hospitals NHS Foundation Trust, UK.
authors.forename: Ian Cjw
authors.initials: IC
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authors.affiliation: Oxford University Hospitals NHS Foundation Trust, UK.
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authors.initials: SJ
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authors.affiliation: Nottingham University Hospitals NHS Trust, UK.
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authors.affiliation: University Hospital of South Manchester NHS Foundation Trust, UK.
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authors.affiliation: University Hospital of South Manchester NHS Foundation Trust, UK.
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authors.affiliation: The Leeds Teaching Hospitals NHS Trust, UK.
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authors.affiliation: Wales Centre for Mycobacteria, UK.
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authors.affiliation: The Royal Liverpool and Broadgreen University Hospitals NHS Trust, UK.
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authors.affiliation: University Hospital of South Manchester NHS Foundation Trust, UK.
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authors.affiliation: Department of Infectious Diseases, Aarhus University Hospital, Denmark.
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authors.affiliation: Department of Infectious Medicine, Institute of Biomedicine, University of Gothenburg, Sweden.
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authors.affiliation: Gartnavel Hospital, Glasgow, NHS Greater Glasgow and Clyde, Scotland, UK.
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authors.affiliation: University Hospitals of Leicester NHS Trust, UK.
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authors.affiliation: The Newcastle upon Tyne Hospitals NHS Foundation Trust, UK.
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authors.affiliation: University of Cambridge Department of Medicine, MRC-Laboratory of Molecular Biology, Cambridge, UK.|Cambridge Centre for Lung Infection, Papworth Hospital, Cambridge, UK.
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mesh_terms: D000818:Animals; D021821:Communicable Diseases, Emerging / Q000453:epidemiology / Q000382:microbiology* / Q000473:pathology / Q000635:transmission; D003550:Cystic Fibrosis / Q000453:epidemiology / Q000382:microbiology* / Q000473:pathology; D024901:Drug Resistance, Multiple, Bacterial; D016680:Genome, Bacterial; D023281:Genomics; D006801:Humans; D015994:Incidence; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D009165:Mycobacterium Infections, Nontuberculous / Q000453:epidemiology / Q000382:microbiology* / Q000473:pathology / Q000635:transmission; D009170:Nontuberculous Mycobacteria / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D010802:Phylogeny; D018410:Pneumonia, Bacterial / Q000453:epidemiology / Q000382:microbiology / Q000473:pathology / Q000635:transmission; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA