title: Building a genomic framework for prospective MRSA surveillance in the United Kingdom and the Republic of Ireland.
abstract: The correct interpretation of microbial sequencing data applied to surveillance and outbreak investigation depends on accessible genomic databases to provide vital genetic context. Our aim was to construct and describe a United Kingdom MRSA database containing over 1000 methicillin-resistant Staphylococcus aureus (MRSA) genomes drawn from England, Northern Ireland, Wales, Scotland, and the Republic of Ireland over a decade. We sequenced 1013 MRSA submitted to the British Society for Antimicrobial Chemotherapy by 46 laboratories between 2001 and 2010. Each isolate was assigned to a regional healthcare referral network in England and was otherwise grouped based on country of origin. Phylogenetic reconstructions were used to contextualize MRSA outbreak investigations and to detect the spread of resistance. The majority of isolates (n = 783, 77%) belonged to CC22, which contains the dominant United Kingdom epidemic clone (EMRSA-15). There was marked geographic structuring of EMRSA-15, consistent with widespread dissemination prior to the sampling decade followed by local diversification. The addition of MRSA genomes from two outbreaks and one pseudo-outbreak demonstrated the certainty with which outbreaks could be confirmed or refuted. We identified local and regional differences in antibiotic resistance profiles, with examples of local expansion, as well as widespread circulation of mobile genetic elements across the bacterial population. We have generated a resource for the future surveillance and outbreak investigation of MRSA in the United Kingdom and Ireland and have shown the value of this during outbreak investigation and tracking of antimicrobial resistance.
authors.affiliation: Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pathogen Genomics, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, United Kingdom;
authors.forename: Sandra
authors.initials: S
authors.lastname: Reuter
authors.affiliation: Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Public Health England, Microbiology Services Division, Addenbrooke's Hospital, Cambridge CB2 0QW, United Kingdom; Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom;
authors.forename: M Estée
authors.initials: ME
authors.lastname: Török
authors.affiliation: Pathogen Genomics, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, United Kingdom; School of Medicine, University of St. Andrews, St. Andrews KY16 9TF, United Kingdom;
authors.forename: Matthew T G
authors.initials: MT
authors.lastname: Holden
authors.affiliation: British Society for Antimicrobial Chemotherapy, B1 3NJ, United Kingdom; North Bristol NHS Trust, Bristol BS10 5NB, United Kingdom;
authors.forename: Rosy
authors.initials: R
authors.lastname: Reynolds
authors.affiliation: Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, United Kingdom;
authors.forename: Kathy E
authors.initials: KE
authors.lastname: Raven
authors.affiliation: Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, United Kingdom;
authors.forename: Beth
authors.initials: B
authors.lastname: Blane
authors.affiliation: Department of Medical Microbiology, University Medical Centre Groningen, Rijksuniversiteit Groningen, 9713 GZ Groningen, The Netherlands;
authors.forename: Tjibbe
authors.initials: T
authors.lastname: Donker
authors.affiliation: Pathogen Genomics, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, United Kingdom;
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.affiliation: Faculty of Medicine, School of Public Health, Imperial College, London W2 1PG, United Kingdom;
authors.forename: David M
authors.initials: DM
authors.lastname: Aanensen
authors.affiliation: Department of Medical Microbiology, University Medical Centre Groningen, Rijksuniversiteit Groningen, 9713 GZ Groningen, The Netherlands; Department of Hospital Epidemiology, Institute for Environmental Medicine and Hospital Hygiene, University Hospital Freiburg, 79106 Freiburg, Germany;
authors.forename: Hajo
authors.initials: H
authors.lastname: Grundmann
authors.affiliation: The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, United Kingdom;
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Feil
authors.affiliation: Faculty of Medicine, School of Public Health, Imperial College, London W2 1PG, United Kingdom;
authors.forename: Brian G
authors.initials: BG
authors.lastname: Spratt
authors.affiliation: Pathogen Genomics, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, United Kingdom;
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pathogen Genomics, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, United Kingdom; Public Health England, Microbiology Services Division, Addenbrooke's Hospital, Cambridge CB2 0QW, United Kingdom; Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom; London School of Hygiene and Tropical Medicine, London, WC1E 7HT, United Kingdom.
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Peacock
mesh_terms: D004196:Disease Outbreaks; D062665:Epidemiological Monitoring; D016680:Genome, Bacterial; D006801:Humans; D007494:Ireland / Q000453:epidemiology; D016106:Methicillin Resistance / Q000235:genetics; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics*; D025202:Molecular Diagnostic Techniques; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000175:diagnosis / Q000453:epidemiology* / Q000382:microbiology; D006113:United Kingdom / Q000453:epidemiology