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

作者：Walden Miriam; Edwards John M; Dziewulska Aleksandra M; Bergmann Rene; Saalbach Gerhard; Kan Su Yin; Miller Ona K; Weckener Miriam; Jackson Rosemary J; Shirran Sally L; Botting Catherine H; Florence Gordon J; Rohde Manfred; Banfield Mark J^*; Schwarz Linek Ulrich

来源：eLife, 2015, 4: e06638.

DOI：10.7554/eLife.06638

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.

• 出版日期2015-6-2