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Here we introduce FibriLysins, a class of engineered enzymes combining staphylokinase and endolysin, which dismantle fibrin-encapsulated multicellular staphylococcal communities, including biofilms and staphylococcal abscess communities (SACs). We characterized diverse staphylokinases, developing a library of 27 FibriLysins, with a 78% positive hit rate. The lead variant, FL-028, has significant antibacterial activity against prevalent clinical\n                    <jats:italic>S. aureus<\/jats:italic>\n                    isolates. In vitro, FL-028 reduced bacterial counts in SACs by 3.4\u2009log and in biofilms by 2.3\u2009log. In vivo, FL-028 exhibits superior efficacy in a mouse model of bone fracture-related infection, outperforming vancomycin by 1\u2009log and eliminating SAC presence in tissues. FL-028 shows no adverse effects on bone healing, as confirmed by histological examination, mechanical testing and micro-computed tomography analyses. These preclinical findings highlight the potential of FibriLysins as a robust and safe therapeutic approach against difficult-to-treat staphylococcal infections.\n                  <\/jats:p>","DOI":"10.1038\/s41564-026-02513-1","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T09:01:49Z","timestamp":1792746109000},"page":"3133-3143","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["FibriLysins disrupt Staphylococcus aureus biofilms and abscess communities"],"prefix":"10.1038","volume":"11","author":[{"given":"Vincent","family":"De Maesschalck","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Chitt\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Siverino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8844-9096","authenticated-orcid":false,"given":"Lena","family":"Gens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8155-4202","authenticated-orcid":false,"given":"Stephan","family":"Zeiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisa","family":"Hangartner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Harz\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1938-254X","authenticated-orcid":false,"given":"Eliane","family":"Vanhoffelen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Van Laere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Kerremans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marleen","family":"Voet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3179-0677","authenticated-orcid":false,"given":"Maarten","family":"Boon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0657-1328","authenticated-orcid":false,"given":"Tine","family":"Van Win","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5633-3993","authenticated-orcid":false,"given":"Greetje","family":"Vande Velde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2185-5724","authenticated-orcid":false,"given":"Jeroen","family":"Wagemans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4114-9093","authenticated-orcid":false,"given":"Willem-Jan","family":"Metsemakers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7778-2480","authenticated-orcid":false,"given":"Robert Geoffrey","family":"Richards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2307-0397","authenticated-orcid":false,"given":"Thomas Fintan","family":"Moriarty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7377-1314","authenticated-orcid":false,"given":"Rob","family":"Lavigne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,23]]},"reference":[{"key":"2513_CR1","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1038\/nrd3975","volume":"12","author":"K Lewis","year":"2013","unstructured":"Lewis, K. 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