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dc.contributor.authorWalden, Miriam
dc.contributor.authorEdwards, John Michael
dc.contributor.authorDziewulska, Aleksandra Malgorzata
dc.contributor.authorBergmann, Rene
dc.contributor.authorSaalbach, Gerhard
dc.contributor.authorKan, Su-Yin
dc.contributor.authorMiller, Ona Kealoha
dc.contributor.authorWeckener, Miriam
dc.contributor.authorJackson, Rosemary J.
dc.contributor.authorShirran, Sally Lorna
dc.contributor.authorBotting, Catherine Helen
dc.contributor.authorFlorence, Gordon John
dc.contributor.authorRohde, Manfred
dc.contributor.authorBanfield, Mark J.
dc.contributor.authorSchwarz-Linek, Uli
dc.date.accessioned2015-06-02T12:10:04Z
dc.date.available2015-06-02T12:10:04Z
dc.date.issued2015-06-02
dc.identifier.citationWalden , M , Edwards , J M , Dziewulska , A M , Bergmann , R , Saalbach , G , Kan , S-Y , Miller , O K , Weckener , M , Jackson , R J , Shirran , S L , Botting , C H , Florence , G J , Rohde , M , Banfield , M J & Schwarz-Linek , U 2015 , ' An internal thioester in a pathogen surface protein mediates covalent host binding ' , eLife , vol. 4 , e06638 . https://doi.org/10.7554/eLife.06638en
dc.identifier.issn2050-084X
dc.identifier.otherPURE: 187656154
dc.identifier.otherPURE UUID: 6d9be525-5339-4fa7-8e7a-d7353e3d7cb1
dc.identifier.otherScopus: 84933047743
dc.identifier.otherORCID: /0000-0003-3516-3507/work/32169110
dc.identifier.otherORCID: /0000-0003-0526-223X/work/40714971
dc.identifier.otherORCID: /0000-0001-9921-4399/work/56638870
dc.identifier.otherWOS: 000374253400001
dc.identifier.urihttp://hdl.handle.net/10023/6727
dc.descriptionThis work was supported by the MRC, UK grant MR/K001485 for MW, JME, MR, MJB, USL; the BBSRC, UK grant BB/J00453 and the John Innes Foundation for MJB; the Wellcome Trust Institutional Strategic Support Fund 097831/Z/11/B for AMD; Wellcome Trust/JIF award 063597 and Wellcome Trust grants WT079272AIA and 094476/Z/10/Z to CHB for the BSRC Mass Spectrometry and Proteomics Facility; University of St Andrews and School of Biology for SYK; The Carnegie Trust for OKM.en
dc.description.abstractTo cause disease and persist in a host, pathogenic and commensal microbes must adhere to tissues. Colonization and infection depend on specific molecular interactions at the host-microbe interface that involve microbial surface proteins, or adhesins. To date, adhesins are only known to bind to host receptors non-covalently. Here we show that the streptococcal surface protein SfbI mediates covalent interaction with the host protein fibrinogen using an unusual internal thioester bond as a ‘chemical harpoon’. This cross-linking reaction allows bacterial attachment to fibrin and SfbI binding to human cells in a model of inflammation. Thioester-containing domains are unexpectedly prevalent in Gram-positive bacteria, including many clinically relevant pathogens. Our findings support bacterial-encoded covalent binding as a new molecular principle in host-microbe interactions. This represents an as yet unexploited target to treat bacterial infection and may also offer novel opportunities for engineering beneficial interactions.
dc.format.extent24
dc.language.isoeng
dc.relation.ispartofeLifeen
dc.rightsCopyright © 2015, Walden et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.en
dc.subjectStreptococcus pyogenesen
dc.subjectStreptococcus pneumoniaeen
dc.subjectClostridium perfringensen
dc.subjectHost-microbe interactionsen
dc.subjectFibrinogenen
dc.subjectBacterial surface proteinsen
dc.subjectQH301 Biologyen
dc.subjectQR Microbiologyen
dc.subjectDASen
dc.subjectBDCen
dc.subjectR2Cen
dc.subject.lccQH301en
dc.subject.lccQRen
dc.titleAn internal thioester in a pathogen surface protein mediates covalent host bindingen
dc.typeJournal articleen
dc.contributor.sponsorMedical Research Councilen
dc.contributor.sponsorThe Wellcome Trusten
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. School of Chemistryen
dc.contributor.institutionUniversity of St Andrews. EaSTCHEMen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.7554/eLife.06638
dc.description.statusPeer revieweden
dc.identifier.grantnumberMR/K001485/1en
dc.identifier.grantnumber094476/Z/10/Zen


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