title: Evolutionary dynamics of methicillin-resistant Staphylococcus aureus within a healthcare system.
abstract: BACKGROUND
  In the past decade, several countries have seen gradual replacement of endemic multi-resistant healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA) with clones that are more susceptible to antibiotic treatment. One example is Singapore, where MRSA ST239, the dominant clone since molecular profiling of MRSA began in the mid-1980s, has been replaced by ST22 isolates belonging to EMRSA-15, a recently emerged pandemic lineage originating from Europe.
  
  
  RESULTS
  We investigated the population structure of MRSA in Singaporean hospitals spanning three decades, using whole genome sequencing. Applying Bayesian phylogenetic methods we report that prior to the introduction of ST22, the ST239 MRSA population in Singapore originated from multiple introductions from the surrounding region; it was frequently transferred within the healthcare system resulting in a heterogeneous hospital population. Following the introduction of ST22 around the beginning of the millennium, this clone spread rapidly through Singaporean hospitals, supplanting the endemic ST239 population. Coalescent analysis revealed that although the genetic diversity of ST239 initially decreased as ST22 became more dominant, from 2007 onwards the genetic diversity of ST239 began to increase once more, which was not associated with the emergence of a sub-clone of ST239. Comparative genomic analysis of the accessory genome of the extant ST239 population identified that the Arginine Catabolic Mobile Element arose multiple times, thereby introducing genes associated with enhanced skin colonization into this population.
  
  
  CONCLUSIONS
  Our results clearly demonstrate that, alongside clinical practice and antibiotic usage, competition between clones also has an important role in driving the evolution of nosocomial pathogen populations.
authors.affiliation: National University Health System, 1E Kent Ridge Road, NUHS Tower Block Level 10, Singapore, 119228, Singapore. liyang_hsu@yahoo.com.|The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 15A, UK. liyang_hsu@yahoo.com.
authors.forename: Li-Yang
authors.initials: LY
authors.lastname: Hsu
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 15A, UK. sh16@sanger.ac.uk.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Harris
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 15A, UK. monikachlebowicz@gmail.com.|University of Groningen, Hanzeplein 1, PO Box 30001, Groningen, 9700 RB, The Netherlands. monikachlebowicz@gmail.com.
authors.forename: Monika A
authors.initials: MA
authors.lastname: Chlebowicz
authors.affiliation: Institute of Infection and Immunity, St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK. jlindsay@sgul.ac.uk.
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Lindsay
authors.affiliation: Singapore General Hospital, Outram Road, Singapore, 169608, Singapore. koh.tse.hsien@sgh.com.sg.
authors.forename: Tse-Hsien
authors.initials: TH
authors.lastname: Koh
authors.affiliation: Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore. prabha_krishnan@ttsh.com.sg.
authors.forename: Prabha
authors.initials: P
authors.lastname: Krishnan
authors.affiliation: Changi General Hospital, 2 Simei Street 3, Singapore, 529889, Singapore. thean_yen_tan@cgh.com.sg.
authors.forename: Thean-Yen
authors.initials: TY
authors.lastname: Tan
authors.affiliation: National University Health System, 1E Kent Ridge Road, NUHS Tower Block Level 10, Singapore, 119228, Singapore. peiyunhon@gmail.com.
authors.forename: Pei-Yun
authors.initials: PY
authors.lastname: Hon
authors.affiliation: Curtin University of Technology, GPO Box U1987, Perth, WA, 6845, Australia. W.Grubb@curtin.edu.au.
authors.forename: Warren B
authors.initials: WB
authors.lastname: Grubb
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 15A, UK. sdb@sangera.ac.uk.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 15A, UK. parkhill@sanger.ac.uk.
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 15A, UK. sjp97@medschl.cam.ac.uk.|University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK. sjp97@medschl.cam.ac.uk.
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Peacock
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 15A, UK. mtgh@st-andrews.ac.uk.|School of Medicine, University of St Andrews, St Andrews, KY16 9TF, UK. mtgh@st-andrews.ac.uk.
authors.forename: Matthew T G
authors.initials: MT
authors.lastname: Holden
mesh_terms: D001499:Bayes Theorem; D003001:Cloning, Molecular; D003428:Cross Infection / Q000453:epidemiology* / Q000382:microbiology; D004269:DNA, Bacterial / Q000235:genetics; D019143:Evolution, Molecular; D015723:Gene Library; D056426:Genetic Loci; D005828:Genetics, Population; D016680:Genome, Bacterial; D006761:Hospitals; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics* / Q000302:isolation & purification; D010802:Phylogeny; D058974:Phylogeography; D017422:Sequence Analysis, DNA; D012846:Singapore / Q000453:epidemiology
chemical_list: D004269:DNA, Bacterial