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

• DOI: 10.7554/elife.06638
• Publication Date: 2015-06-01T08:39:59Z
• Authors: Miriam Walden; John M Edwards; Aleksandra M Dzie...; Rene Bergmann; Gerhard Saalbach; Su-Yin Kan; Ona K Miller; Miriam Weckener; Rosemary J Jackson; Sally L Shirran; Catherine H Botting; Gordon J Florence; Manfred Rohde; Mark J Banfield; Ulrich Schwarz-Linek
• Keywords: 570; host-microbe interaction; Streptococcus pyogenes; Clostridium perfringens; QH301-705.5; QH301 Biology; Science; 610; QH301; 03 medical and health sciences; SDG 3 - Good Health and Well-being; Escherichia coli; Humans; Biology (General); Adhesins, Bacterial; R2C; Inflammation; Fibrin; 0303 health sciences; Bacterial surface proteins; Host-microbe interactions; Q; R; Fibrinogen; Membrane Proteins; DAS; QR Microbiology; Biophysics and Structural Biology; QR; 3. Good health; Streptococcus pneumoniae; bacterial surface protein; Medicine; fibrinogen; BDC; Carrier Proteins

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.