Molecular tracing of the emergence, adaptation, and transmission of hospital-associated methicillin-resistant Staphylococcus aureus.
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Abstract | 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. |
Year of Publication | 2012
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Journal | Proc Natl Acad Sci U S A
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Volume | 109
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Issue | 23
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Pages | 9107-12
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Date Published | 2012 Jun 05
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ISSN | 1091-6490
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DOI | 10.1073/pnas.1202869109
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PubMed ID | 22586109
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PubMed Central ID | PMC3384211
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Grant list | 089472 / 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
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