An internal thioester in a pathogen surface protein mediates covalent host binding
MetadataShow full item record
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.
Walden , 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.06638
Copyright © 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.