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Proc Natl Acad Sci U S A DOI:10.1073/pnas.1202869109

Molecular tracing of the emergence, adaptation, and transmission of hospital-associated methicillin-resistant Staphylococcus aureus.

Publication TypeJournal Article
Year of Publication2012
AuthorsMcAdam, PR, Templeton, KE, Edwards, GF, Holden, MTG, Feil, EJ, Aanensen, DM, Bargawi, HJA, Spratt, BG, Bentley, SD, Parkhill, J, Enright, MC, Holmes, A, E Girvan, K, Godfrey, PA, Feldgarden, M, Kearns, AM, Rambaut, A, D Robinson, A, J Fitzgerald, R
JournalProc Natl Acad Sci U S A
Date Published2012 Jun 05
KeywordsBase Sequence, Bayes Theorem, Cross Infection, Genome, Bacterial, Humans, Methicillin-Resistant Staphylococcus aureus, Models, Genetic, Molecular Sequence Data, Phylogeny, Phylogeography, Sequence Alignment, Sequence Analysis, DNA, Species Specificity, Staphylococcal Infections, United Kingdom, Virulence

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.


Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID22586109
PubMed Central IDPMC3384211
Grant List089472 / / Wellcome Trust / United Kingdom
HHSN272200900018C / AI / NIAID NIH HHS / United States
GM080602 / GM / NIGMS NIH HHS / United States
/ / Medical Research Council / United Kingdom
/ / Biotechnology and Biological Sciences Research Council / United Kingdom
CZB/4/717 / / Chief Scientist Office / United Kingdom
R01 GM080602 / GM / NIGMS NIH HHS / United States
MR/K001744/1 / / Medical Research Council / United Kingdom
095831 / / Wellcome Trust / United Kingdom
HHSN272200900018C / / PHS HHS / United States
098051 / / Wellcome Trust / United Kingdom
/ / Chief Scientist Office / United Kingdom