title: A genomic portrait of the emergence, evolution, and global spread of a methicillin-resistant Staphylococcus aureus pandemic.
abstract: The widespread use of antibiotics in association with high-density clinical care has driven the emergence of drug-resistant bacteria that are adapted to thrive in hospitalized patients. Of particular concern are globally disseminated methicillin-resistant Staphylococcus aureus (MRSA) clones that cause outbreaks and epidemics associated with health care. The most rapidly spreading and tenacious health-care-associated clone in Europe currently is EMRSA-15, which was first detected in the UK in the early 1990s and subsequently spread throughout Europe and beyond. Using phylogenomic methods to analyze the genome sequences for 193 S. aureus isolates, we were able to show that the current pandemic population of EMRSA-15 descends from a health-care-associated MRSA epidemic that spread throughout England in the 1980s, which had itself previously emerged from a primarily community-associated methicillin-sensitive population. The emergence of fluoroquinolone resistance in this EMRSA-15 subclone in the English Midlands during the mid-1980s appears to have played a key role in triggering pandemic spread, and occurred shortly after the first clinical trials of this drug. Genome-based coalescence analysis estimated that the population of this subclone over the last 20 yr has grown four times faster than its progenitor. Using comparative genomic analysis we identified the molecular genetic basis of 99.8% of the antimicrobial resistance phenotypes of the isolates, highlighting the potential of pathogen genome sequencing as a diagnostic tool. We document the genetic changes associated with adaptation to the hospital environment and with increasing drug resistance over time, and how MRSA evolution likely has been influenced by country-specific drug use regimens.
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB19 1SA, United Kingdom.
authors.forename: Matthew T G
authors.initials: MT
authors.lastname: Holden
authors.forename: Li-Yang
authors.initials: LY
authors.lastname: Hsu
authors.forename: Kevin
authors.initials: K
authors.lastname: Kurt
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Weinert
authors.forename: Alison E
authors.initials: AE
authors.lastname: Mather
authors.forename: Simon R
authors.initials: SR
authors.lastname: Harris
authors.forename: Birgit
authors.initials: B
authors.lastname: Strommenger
authors.forename: Franziska
authors.initials: F
authors.lastname: Layer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Witte
authors.forename: Herminia
authors.initials: H
authors.lastname: de Lencastre
authors.forename: Robert
authors.initials: R
authors.lastname: Skov
authors.forename: Henrik
authors.initials: H
authors.lastname: Westh
authors.forename: Helena
authors.initials: H
authors.lastname: Zemlicková
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Coombs
authors.forename: Angela M
authors.initials: AM
authors.lastname: Kearns
authors.forename: Robert L R
authors.initials: RL
authors.lastname: Hill
authors.forename: Jonathan
authors.initials: J
authors.lastname: Edgeworth
authors.forename: Ian
authors.initials: I
authors.lastname: Gould
authors.forename: Vanya
authors.initials: V
authors.lastname: Gant
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cooke
authors.forename: Giles F
authors.initials: GF
authors.lastname: Edwards
authors.forename: Paul R
authors.initials: PR
authors.lastname: McAdam
authors.forename: Kate E
authors.initials: KE
authors.lastname: Templeton
authors.forename: Angela
authors.initials: A
authors.lastname: McCann
authors.forename: Zhemin
authors.initials: Z
authors.lastname: Zhou
authors.forename: Santiago
authors.initials: S
authors.lastname: Castillo-Ramírez
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Feil
authors.forename: Lyndsey O
authors.initials: LO
authors.lastname: Hudson
authors.forename: Mark C
authors.initials: MC
authors.lastname: Enright
authors.forename: Francois
authors.initials: F
authors.lastname: Balloux
authors.forename: David M
authors.initials: DM
authors.lastname: Aanensen
authors.forename: Brian G
authors.initials: BG
authors.lastname: Spratt
authors.forename: J Ross
authors.initials: JR
authors.lastname: Fitzgerald
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.forename: Mark
authors.initials: M
authors.lastname: Achtman
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.forename: Ulrich
authors.initials: U
authors.lastname: Nübel
mesh_terms: D016000:Cluster Analysis; D024881:Drug Resistance, Bacterial / Q000235:genetics; D016680:Genome, Bacterial; D023281:Genomics; D005838:Genotype; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000145:classification / Q000235:genetics*; D058873:Pandemics; D010802:Phylogeny; D058974:Phylogeography; D013203:Staphylococcal Infections / Q000453:epidemiology* / Q000635:transmission; D006113:United Kingdom / Q000453:epidemiology