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dc.contributor.authorBrouwer, Stephan
dc.contributor.authorBarnett, Timothy C.
dc.contributor.authorLy, Diane
dc.contributor.authorKasper, Katherine J.
dc.contributor.authorDe Oliveira, David M. P.
dc.contributor.authorRivera-Hernandez, Tania
dc.contributor.authorCork, Amanda J.
dc.contributor.authorMcIntyre, Liam
dc.contributor.authorJespersen, Magnus G.
dc.contributor.authorRichter, Johanna
dc.contributor.authorSchulz, Benjamin L.
dc.contributor.authorDougan, Gordon
dc.contributor.authorNizet, Victor
dc.contributor.authorYuen, Kwok-Yung
dc.contributor.authorYou, Yuanhai
dc.contributor.authorMcCormick, John K.
dc.contributor.authorSanderson-Smith, Martina L.
dc.contributor.authorDavies, Mark R.
dc.contributor.authorWalker, Mark J.
dc.date.accessioned2020-10-06T15:09:22Z
dc.date.available2020-10-06T15:09:22Z
dc.date.issued2020-10-06
dc.date.submitted2019-12-21
dc.identifier.others41467-020-18700-5
dc.identifier.other18700
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/311142
dc.description.abstractAbstract: The re-emergence of scarlet fever poses a new global public health threat. The capacity of North-East Asian serotype M12 (emm12) Streptococcus pyogenes (group A Streptococcus, GAS) to cause scarlet fever has been linked epidemiologically to the presence of novel prophages, including prophage ΦHKU.vir encoding the secreted superantigens SSA and SpeC and the DNase Spd1. Here, we report the molecular characterization of ΦHKU.vir-encoded exotoxins. We demonstrate that streptolysin O (SLO)-induced glutathione efflux from host cellular stores is a previously unappreciated GAS virulence mechanism that promotes SSA release and activity, representing the first description of a thiol-activated bacterial superantigen. Spd1 is required for resistance to neutrophil killing. Investigating single, double and triple isogenic knockout mutants of the ΦHKU.vir-encoded exotoxins, we find that SpeC and Spd1 act synergistically to facilitate nasopharyngeal colonization in a mouse model. These results offer insight into the pathogenesis of scarlet fever-causing GAS mediated by prophage ΦHKU.vir exotoxins.
dc.languageen
dc.publisherNature Publishing Group UK
dc.subjectArticle
dc.subject/631/326/1320
dc.subject/692/420/254
dc.subject/13/1
dc.subject/13/106
dc.subject/14/34
dc.subject/14/63
dc.subject/38/1
dc.subject/38/22
dc.subject/38/91
dc.subject/38/39
dc.subject/38/77
dc.subject/38/70
dc.subject/64/110
dc.subject/82/80
dc.subject/82/83
dc.subject/82/29
dc.subjectarticle
dc.titleProphage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes
dc.typeArticle
dc.date.updated2020-10-06T15:09:21Z
prism.issueIdentifier1
prism.publicationNameNature Communications
prism.volume11
dc.identifier.doi10.17863/CAM.58232
dcterms.dateAccepted2020-09-01
rioxxterms.versionofrecord10.1038/s41467-020-18700-5
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidBarnett, Timothy C. [0000-0002-3346-5117]
dc.contributor.orcidDe Oliveira, David M. P. [0000-0002-5085-7163]
dc.contributor.orcidJespersen, Magnus G. [0000-0001-9751-9877]
dc.contributor.orcidNizet, Victor [0000-0003-3847-0422]
dc.contributor.orcidYuen, Kwok-Yung [0000-0002-2083-1552]
dc.contributor.orcidMcCormick, John K. [0000-0003-3742-7289]
dc.contributor.orcidSanderson-Smith, Martina L. [0000-0002-6366-4993]
dc.contributor.orcidDavies, Mark R. [0000-0001-6141-5179]
dc.contributor.orcidWalker, Mark J. [0000-0001-7423-2769]
dc.identifier.eissn2041-1723
pubs.funder-project-idDepartment of Health | National Health and Medical Research Council (NHMRC) (1126805)


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