A Host Defense Role for Fibrinogen by Direct Binding of Clostridium botulinum C2 toxin

A Host Defense Role for Fibrinogen by Direct Binding of Clostridium botulinum C2 toxin | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A Host Defense Role for Fibrinogen by Direct Binding of Clostridium botulinum C2 toxin Sophia Kistermann, Sebastian Heber, Stephan Fischer, Jannik Sichau, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8899831/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract 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 Clostridium (C.) botulinum C2 toxin. Our results indicate that fibrinogen specifically interacts with the binding subunit of C2 toxin in vitro. This prevents receptor-binding and cellular uptake of the toxin. Related toxins from Bacillus anthracis (lethal toxin), C. perfringens (iota) or Clostridioides difficile (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. Bacterial protein toxin blood coagulation factor C2 toxin Clostridium botulinum fibrinogen toxin inhibitor Full Text Supplementary Files 2026SupplementCMLS.pdf Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 24 Feb, 2026 Reviewers invited by journal 19 Feb, 2026 Editor assigned by journal 18 Feb, 2026 First submitted to journal 16 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8899831","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":593975331,"identity":"4590525e-9591-49b6-9a3c-858fb57448e6","order_by":0,"name":"Sophia Kistermann","email":"","orcid":"","institution":"Ulm University Medical Center: Universitatsklinikum Ulm","correspondingAuthor":false,"prefix":"","firstName":"Sophia","middleName":"","lastName":"Kistermann","suffix":""},{"id":593975332,"identity":"4498bd2a-186a-45e9-bb49-6a26cad46f01","order_by":1,"name":"Sebastian Heber","email":"","orcid":"","institution":"Ulm University Hospital: 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