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dc.contributor.authorLaabei, Maisem
dc.contributor.authorRecker, Mario
dc.contributor.authorRudkin, Justine K.
dc.contributor.authorAldeljawi, Mona
dc.contributor.authorGulay, Zeynep
dc.contributor.authorSloan, Tim J.
dc.contributor.authorWilliams, Paul
dc.contributor.authorEndres, Jennifer L.
dc.contributor.authorBayles, Kenneth W.
dc.contributor.authorFey, Paul D.
dc.contributor.authorYajjala, Vijaya Kumar
dc.contributor.authorWidhelm, Todd
dc.contributor.authorHawkins, Erica
dc.contributor.authorLewis, Katie
dc.contributor.authorParfett, Sara
dc.contributor.authorScowen, Lucy
dc.contributor.authorPeacock, Sharon J.
dc.contributor.authorHolden, Matthew
dc.contributor.authorWilson, Daniel
dc.contributor.authorRead, Timothy D.
dc.contributor.authorvan den Elsen, Jean
dc.contributor.authorPriest, Nicholas K.
dc.contributor.authorFeil, Edward J.
dc.contributor.authorHurst, Laurence D.
dc.contributor.authorJosefsson, Elisabet
dc.contributor.authorMassey, Ruth C.
dc.date.accessioned2014-09-26T15:00:45Z
dc.date.issued2014-04-09
dc.description.abstractMicrobial virulence is a complex and often multifactorial phenotype, intricately linked to a pathogen’s evolutionary trajectory. Toxicity, the ability to destroy host cell membranes, and adhesion, the ability to adhere to human tissues, are the major virulence factors of many bacterial pathogens, including Staphylococcus aureus. Here, we assayed the toxicity and adhesiveness of 90 MRSA (methicillin resistant S. aureus) isolates and found that while there was remarkably little variation in adhesion, toxicity varied by over an order of magnitude between isolates, suggesting different evolutionary selection pressures acting on these two traits. We performed a genome-wide association study (GWAS) and identified a large number of loci, as well as a putative network of epistatically interacting loci, that significantly associated with toxicity. Despite this apparent complexity in toxicity regulation, a predictive model based on a set of significant single nucleotide polymorphisms (SNPs) and insertion and deletions events (indels) showed a high degree of accuracy in predicting an isolate’s toxicity solely from the genetic signature at these sites. Our results thus highlight the potential of using sequence data to determine clinically relevant parameters and have further implications for understanding the microbial virulence of this opportunistic pathogen.en_GB
dc.description.sponsorshipC-FP7 program no. 245500en_GB
dc.description.sponsorshipBiotechnology and Biological Sciences Research Council (BBSRC)en_GB
dc.description.sponsorshipRoyal Societyen_GB
dc.identifier.citationVol. 24 (5), pp. 839 - 849en_GB
dc.identifier.doi10.1101/gr.165415.113
dc.identifier.urihttp://hdl.handle.net/10871/15644
dc.language.isoenen_GB
dc.publisherCold Spring Harbor Laboratory Pressen_GB
dc.rights.embargoreasonPublisher policyen_GB
dc.rightsThis article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0.en_GB
dc.titlePredicting the virulence of MRSA from its genome sequenceen_GB
dc.typeArticleen_GB
dc.date.available2014-10-09T03:00:10Z
dc.identifier.issn1088-9051
dc.identifier.eissn1549-5469
dc.identifier.journalGenome Researchen_GB


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