title: Identification of source and sink populations for the emergence and global spread of the East-Asia clone of community-associated MRSA.
abstract: Our understanding of the factors influencing the emergence, dissemination and global distribution of epidemic clones of bacteria is limited. ST59 is a major epidemic clone of community-associated MRSA in East Asia, responsible for extensive morbidity and mortality, but has a much lower prevalence in other parts of the world. The geographic origin of ST59 and its international routes of dissemination are unclear and disputed in the literature.
  
  
  
  To investigate the origin and spread of the ST59 clone, we obtained whole genome sequences of isolates from four continents, sampled over more than a decade, and carried out a time-scaled phylogeographic analysis. We discover that two distinct ST59 clades emerged concurrently, in East Asia and the USA, but underwent clonal expansion at different times. The East Asia clade was strongly enriched for gene determinants associated with antibiotic resistance, consistent with regional differences in antibiotic usage. Both clones spread independently to Australia and Europe, and we found evidence of the persistence of multi-drug resistance following export from East Asia. Direct transfer of strains between Taiwan and the USA was not observed in either direction, consistent with geographic niche exclusion.
  
  
  
  Our results resolve a longstanding controversy regarding the origin of the ST59 clone, revealing the major global source and sink populations and routes for the spread of multi-drug resistant clones. Additionally, our findings indicate that diversification of the accessory genome of epidemic clones partly reflects region-specific patterns of antibiotic usage, which may influence bacterial fitness after transmission to different geographic locations.
authors.affiliation: Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, UK.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Ward
authors.affiliation: The Roslin Institute, University of Edinburgh, Edinburgh, UK.
authors.forename: Mariya
authors.initials: M
authors.lastname: Goncheva
authors.affiliation: The Roslin Institute, University of Edinburgh, Edinburgh, UK.
authors.forename: Emily
authors.initials: E
authors.lastname: Richardson
authors.affiliation: The Roslin Institute, University of Edinburgh, Edinburgh, UK.
authors.forename: Paul R
authors.initials: PR
authors.lastname: McAdam
authors.affiliation: The Roslin Institute, University of Edinburgh, Edinburgh, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Raftis
authors.affiliation: Public Health England, Colindale, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Kearns
authors.affiliation: University of Chicago, Chicago, IL, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Daum
authors.affiliation: University of Chicago, Chicago, IL, USA.
authors.forename: Michael Z
authors.initials: MZ
authors.lastname: David
authors.affiliation: National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Tsai Ling
authors.initials: TL
authors.lastname: Lauderdale
authors.affiliation: Scottish MRSA Reference Laboratory, NHS Greater Glasgow and Clyde, Glasgow, UK.
authors.forename: Giles F
authors.initials: GF
authors.lastname: Edwards
authors.affiliation: Griffith University School of Medicine, Gold Coast, QLD, Australia.
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Nimmo
authors.affiliation: Australian Collaborating Centre for Enterococcus and Staphylococcus Species (ACCESS) Typing and Research, Murdoch University, Perth, Australia.
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Coombs
authors.affiliation: National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors.forename: Xander
authors.initials: X
authors.lastname: Huijsdens
authors.affiliation: Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, UK.
authors.forename: Mark E J
authors.initials: ME
authors.lastname: Woolhouse
authors.affiliation: The Roslin Institute, University of Edinburgh, Edinburgh, UK. Ross.Fitzgerald@ed.ac.uk.
authors.forename: J Ross
authors.identifier: 0000-0002-9233-8468
authors.initials: JR
authors.lastname: Fitzgerald
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001208:Asia / Q000453:epidemiology; D017714:Community-Acquired Infections / Q000453:epidemiology* / Q000382:microbiology*; D024881:Drug Resistance, Bacterial; D005798:Genes, Bacterial; D005838:Genotype; D014943:Global Health; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000235:genetics*; D010802:Phylogeny; D058974:Phylogeography; D062486:Public Health Surveillance; D013203:Staphylococcal Infections / Q000453:epidemiology* / Q000382:microbiology*; D014481:United States / Q000453:epidemiology
chemical_list: D000900:Anti-Bacterial Agents