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An internal thioester in a pathogen surface protein mediates covalent host binding

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Author(s)

Miriam Walden, John Michael Edwards, Aleksandra Malgorzata Dziewulska, Rene Bergmann, Gerhard Saalbach, Su-Yin Kan, Ona Kealoha Miller, Miriam Weckener, Rosemary J. Jackson, Sally Lorna Shirran, Catherine Helen Botting, Gordon John Florence, Manfred Rohde, Mark J. Banfield, Uli Schwarz-Linek

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Abstract

To 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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Original languageEnglish
Article numbere06638
Number of pages24
JournaleLife
Volume4
DOIs
Publication statusPublished - 2 Jun 2015

    Research areas

  • Streptococcus pyogenes, Streptococcus pneumoniae, Clostridium perfringens, Host-microbe interactions, Fibrinogen, Bacterial surface proteins

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