title: Molecular tracing of the emergence, adaptation, and transmission of hospital-associated methicillin-resistant Staphylococcus aureus.
abstract: Hospital-associated infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a global health burden dominated by a small number of bacterial clones. The pandemic EMRSA-16 clone (ST36-II) has been widespread in UK hospitals for 20 y, but its evolutionary origin and the molecular basis for its hospital association are unclear. We carried out a Bayesian phylogenetic reconstruction on the basis of the genome sequences of 87 S. aureus isolates including 60 EMRSA-16 and 27 additional clonal complex 30 (CC30) isolates, collected from patients in three continents over a 53-y period. The three major pandemic clones to originate from the CC30 lineage, including phage type 80/81, Southwest Pacific, and EMRSA-16, shared a most recent common ancestor that existed over 100 y ago, whereas the hospital-associated EMRSA-16 clone is estimated to have emerged about 35 y ago. Our CC30 genome-wide analysis revealed striking molecular correlates of hospital- or community-associated pandemics represented by mobile genetic elements and nonsynonymous mutations affecting antibiotic resistance and virulence. Importantly, phylogeographic analysis indicates that EMRSA-16 spread within the United Kingdom by transmission from hospitals in large population centers in London and Glasgow to regional health-care settings, implicating patient referrals as an important cause of nationwide transmission. Taken together, the high-resolution phylogenomic approach used resulted in a unique understanding of the emergence and transmission of a major MRSA clone and provided molecular correlates of its hospital adaptation. Similar approaches for hospital-associated clones of other bacterial pathogens may inform appropriate measures for controlling their intra- and interhospital spread.
authors.affiliation: The Roslin Institute and Edinburgh Infectious Diseases, Royal (Dick) School of Veterinary Studies,  University of Edinburgh, Midlothian EH259RG,  United Kingdom.
authors.forename: Paul R
authors.initials: PR
authors.lastname: McAdam
authors.forename: Kate E
authors.initials: KE
authors.lastname: Templeton
authors.forename: Giles F
authors.initials: GF
authors.lastname: Edwards
authors.forename: Matthew T G
authors.initials: MT
authors.lastname: Holden
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Feil
authors.forename: David M
authors.initials: DM
authors.lastname: Aanensen
authors.forename: Hiba J A
authors.initials: HJ
authors.lastname: Bargawi
authors.forename: Brian G
authors.initials: BG
authors.lastname: Spratt
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.forename: Mark C
authors.initials: MC
authors.lastname: Enright
authors.forename: Anne
authors.initials: A
authors.lastname: Holmes
authors.forename: E Kirsty
authors.initials: EK
authors.lastname: Girvan
authors.forename: Paul A
authors.initials: PA
authors.lastname: Godfrey
authors.forename: Michael
authors.initials: M
authors.lastname: Feldgarden
authors.forename: Angela M
authors.initials: AM
authors.lastname: Kearns
authors.forename: Andrew
authors.initials: A
authors.lastname: Rambaut
authors.forename: D Ashley
authors.initials: DA
authors.lastname: Robinson
authors.forename: J Ross
authors.initials: JR
authors.lastname: Fitzgerald
mesh_terms: D001483:Base Sequence; D001499:Bayes Theorem; D003428:Cross Infection / Q000635:transmission*; D016680:Genome, Bacterial / Q000235:genetics*; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics* / Q000472:pathogenicity; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010802:Phylogeny; D058974:Phylogeography; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D013203:Staphylococcal Infections / Q000453:epidemiology* / Q000635:transmission*; D006113:United Kingdom / Q000453:epidemiology; D014774:Virulence