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dc.contributor.authorChua, KYL
dc.contributor.authorMonk, IR
dc.contributor.authorLin, Y-H
dc.contributor.authorSeemann, T
dc.contributor.authorTuck, KL
dc.contributor.authorPorter, JL
dc.contributor.authorStepnell, J
dc.contributor.authorCoombs, GW
dc.contributor.authorDavies, JK
dc.contributor.authorStinear, TP
dc.contributor.authorHowden, BP
dc.date.available2019-02-13T19:00:10Z
dc.date.available2014-02-05
dc.date.available2014-02-05
dc.date.available2014-02-05
dc.date.available2014-02-05
dc.date.issued2014-02-10
dc.identifierpii: 1471-2180-14-31
dc.identifier.citationChua, K. Y. L., Monk, I. R., Lin, Y. -H., Seemann, T., Tuck, K. L., Porter, J. L., Stepnell, J., Coombs, G. W., Davies, J. K., Stinear, T. P. & Howden, B. P. (2014). Hyperexpression of alpha-hemolysin explains enhanced virulence of sequence type 93 community-associated methicillin-resistant Staphylococcus aureus. BMC MICROBIOLOGY, 14 (1), https://doi.org/10.1186/1471-2180-14-31.
dc.identifier.issn1471-2180
dc.identifier.urihttp://hdl.handle.net/11343/220650
dc.description.abstractBACKGROUND: The community-associated methicillin-resistant S. aureus (CA-MRSA) ST93 clone is becoming dominant in Australia and is clinically highly virulent. In addition, sepsis and skin infection models demonstrate that ST93 CA-MRSA is the most virulent global clone of S. aureus tested to date. While the determinants of virulence have been studied in other clones of CA-MRSA, the basis for hypervirulence in ST93 CA-MRSA has not been defined. RESULTS: Here, using a geographically and temporally dispersed collection of ST93 isolates we demonstrate that the ST93 population hyperexpresses key CA-MRSA exotoxins, in particular α-hemolysin, in comparison to other global clones. Gene deletion and complementation studies, and virulence comparisons in a murine skin infection model, showed unequivocally that increased expression of α-hemolysin is the key staphylococcal virulence determinant for this clone. Genome sequencing and comparative genomics of strains with divergent exotoxin profiles demonstrated that, like other S. aureus clones, the quorum sensing agr system is the master regulator of toxin expression and virulence in ST93 CA-MRSA. However, we also identified a previously uncharacterized AraC/XylS family regulator (AryK) that potentiates toxin expression and virulence in S. aureus. CONCLUSIONS: These data demonstrate that hyperexpression of α-hemolysin mediates enhanced virulence in ST93 CA-MRSA, and additional control of exotoxin production, in particular α-hemolysin, mediated by regulatory systems other than agr have the potential to fine-tune virulence in CA-MRSA.
dc.languageEnglish
dc.publisherBMC
dc.titleHyperexpression of alpha-hemolysin explains enhanced virulence of sequence type 93 community-associated methicillin-resistant Staphylococcus aureus
dc.typeJournal Article
dc.identifier.doi10.1186/1471-2180-14-31
melbourne.affiliation.departmentClinical School (Austin Health)
melbourne.affiliation.departmentMicrobiology and Immunology
melbourne.source.titleBMC MICROBIOLOGY
melbourne.source.volume14
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1235888
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3922988
melbourne.contributor.authorHowden, Benjamin
melbourne.contributor.authorChua, Kyra
melbourne.contributor.authorLIN, YA-HSUN
melbourne.contributor.authorStinear, Timothy
melbourne.contributor.authorPorter, Jessica
melbourne.contributor.authorStepnell, Justin
melbourne.contributor.authorMonk, Ian
melbourne.contributor.authorSeemann, Torsten
dc.identifier.eissn1471-2180
melbourne.conference.locationEngland
pubs.acceptance.date2014-02-05
melbourne.accessrightsOpen Access


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