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Life Sci."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    In addition to fibrinogens canonical function in hemostasis, alternate roles in innate immunity have emerged. However, interactions with bacterial protein toxins, the main virulence factors of many medically relevant bacteria and causative agents of life-threatening diseases, have not been described so far. Here, we identified human fibrinogen as an inhibitor of the enterotoxic\n                    <jats:italic>Clostridium<\/jats:italic>\n                    (\n                    <jats:italic>C.<\/jats:italic>\n                    )\n                    <jats:italic>botulinum<\/jats:italic>\n                    C2 toxin. Our results indicate that fibrinogen specifically interacts with the binding subunit of C2 toxin in vitro and that N-linked glycans of fibrinogen are crucial for this interaction. This prevents receptor-binding and cellular uptake of the toxin. Related toxins from\n                    <jats:italic>Bacillus anthracis<\/jats:italic>\n                    (lethal toxin),\n                    <jats:italic>C. perfringens<\/jats:italic>\n                    (iota) or\n                    <jats:italic>Clostridioides difficile<\/jats:italic>\n                    (CDT) do not bind to fibrinogen and are therefore not inhibited. Furthermore, C2 toxin had no effect on coagulation of human blood ex vivo. In conclusion, we identified fibrinogen as an inhibitor of a highly potent bacterial protein toxin, highlighting an unexpected role for this blood coagulation factor in innate immunity.\n                  <\/jats:p>","DOI":"10.1007\/s00018-026-06253-7","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T07:45:02Z","timestamp":1779176702000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A host defense role for Fibrinogen by direct binding of Clostridium botulinum C2 toxin"],"prefix":"10.1007","volume":"83","author":[{"given":"Sophia","family":"Kistermann","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Heber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jannik","family":"Sichau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph Q.","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Mannes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Huber-Lang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2706-3402","authenticated-orcid":false,"given":"Holger","family":"Barth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"6253_CR1","doi-asserted-by":"publisher","first-page":"182","DOI":"10.3390\/toxins16040182","volume":"16","author":"MR Popoff","year":"2024","unstructured":"Popoff MR (2024) Overview of Bacterial Protein Toxins from Pathogenic Bacteria: Mode of Action and Insights into Evolution. 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