Building a genomic framework for prospective MRSA surveillance in the United Kingdom and the Republic of Ireland

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 UK MRSA database containing over 1,000 methicillin-resistant Staphylococcus aureus (MRSA) genomes drawn from England, Northern Ireland, Wales, Scotland and the Republic of Ireland over a decade. We sequenced 1,013 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 otherwise grouped based on country of origin. Phylogenetic reconstructions were used to contextualise MRSA outbreak investigations, and to detect the spread of resistance. The majority of isolates (n=783, 77%) belonged to CC22, which contains the dominant UK 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 UK and Ireland, and have shown the value of this during outbreak investigation and tracking of antimicrobial resistance.