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dc.contributor.authorWalden, Miriam*
dc.contributor.authorEdwards, John M*
dc.contributor.authorDziewulska, Aleksandra M*
dc.contributor.authorBergmann, Rene*
dc.contributor.authorSaalbach, Gerhard*
dc.contributor.authorKan, Su-Yin*
dc.contributor.authorMiller, Ona K*
dc.contributor.authorWeckener, Miriam*
dc.contributor.authorJackson, Rosemary J*
dc.contributor.authorShirran, Sally L*
dc.contributor.authorBotting, Catherine H*
dc.contributor.authorFlorence, Gordon J*
dc.contributor.authorRohde, Manfred*
dc.contributor.authorBanfield, Mark J*
dc.contributor.authorSchwarz-Linek, Ulrich*
dc.date.accessioned2015-06-15T14:10:13Zen
dc.date.available2015-06-15T14:10:13Zen
dc.date.issued2015en
dc.identifier.citationAn internal thioester in a pathogen surface protein mediates covalent host binding. 2015, 4: Elifeen
dc.identifier.issn2050-084Xen
dc.identifier.pmid26032562en
dc.identifier.doi10.7554/eLife.06638en
dc.identifier.urihttp://hdl.handle.net/10033/556926en
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.language.isoenen
dc.titleAn internal thioester in a pathogen surface protein mediates covalent host binding.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany.en
dc.identifier.journaleLifeen
refterms.dateFOA2018-06-12T16:41:23Z
html.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.


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