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

Miriam Walden, John Michael Edwards, Aleksandra Malgorzata Dziewulska, Rene Bergmann, Gerhard Saalbach, Su-Yin Kan, Ona Kealoha Miller, Miriam Weckener, Rosemary J. Jackson, Sally Lorna Shirran, Catherine Helen Botting, Gordon John Florence, Manfred Rohde, Mark J. Banfield, Uli Schwarz-Linek

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

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.
Original languageEnglish
Article numbere06638
Number of pages24
JournaleLife
Volume4
DOIs
Publication statusPublished - 2 Jun 2015

Keywords

  • Streptococcus pyogenes
  • Streptococcus pneumoniae
  • Clostridium perfringens
  • Host-microbe interactions
  • Fibrinogen
  • Bacterial surface proteins

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