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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.

Original publication

DOI

10.1073/pnas.1202869109

Type

Journal article

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Date

06/2012

Volume

109

Pages

9107 - 9112

Addresses

The Roslin Institute and Edinburgh Infectious Diseases, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian EH259RG, United Kingdom.

Keywords

Humans, Staphylococcal Infections, Cross Infection, Bayes Theorem, Sequence Alignment, Sequence Analysis, DNA, Phylogeny, Virulence, Species Specificity, Base Sequence, Genome, Bacterial, Models, Genetic, Molecular Sequence Data, Methicillin-Resistant Staphylococcus aureus, Phylogeography, United Kingdom