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

• Main Authors: Su-yin, Kan, Miriam, Walden, John M, Edwards
• Format: Article
• Language: English
• Published: 2015
• Subjects: QH301 Biology
• Online Access: http://eprints.unisza.edu.my/6442/1/FH02-FSK-15-03509.jpg; http://eprints.unisza.edu.my/6442/
• Institution: Universiti Sultan Zainal Abidin

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.