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

Walden, Miriam and Edwards, John and Dziewulska, Aleksandra and Bergmann, Rene and Saalbach, Gerhard and Kan, Su-Yin and Miller, Ona and Weckener, Miriam and Jackson, Rosemary and Shirran, Sally and Botting, Catherine and Florence, Gordon and Rohde, Manfred and Banfield, Mark and Schwarz-Linek, Ulrich (2015) An internal thioester in a pathogen surface protein mediates covalent host binding. eLIFE, 4 (e06638). pp. 1-24. ISSN 2050-084X

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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.

Item Type: Article
Subjects: Q Science > QR Microbiology
Faculty / Institute: Faculty Of Health Sciences
Depositing User: Dr. Su-Yin Kan
Date Deposited: 02 Aug 2015 08:00
Last Modified: 27 Dec 2015 06:46

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