{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T22:23:13Z","timestamp":1787350993527,"version":"build-2736575974"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    Anti-staphylococcal lytic agents, such as lysostaphin (LSN), a glycyl-glycyl (Gly-Gly) peptidase, have long been considered for the management of chronic and complicated bacterial infections typically resistant to conventional antibiotics, but their use is restricted by poor pharmacokinetic properties. We generated half-life extended lysostaphin constructs by fusing the lysin - either alone or chimerized with an additional enzymatic cysteine, histidine-dependent amidohydrolases\/peptidases (CHAP) domain - to the human IgG1 Fc fragment. The Fc-CHAP-LSN constructs retain high potency against\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    and coagulase negative staphylococcal strains\n                    <jats:italic>in vitro<\/jats:italic>\n                    and are efficacious in\n                    <jats:italic>S. aureus ex vivo<\/jats:italic>\n                    biofilm models and\n                    <jats:italic>in vivo<\/jats:italic>\n                    sepsis models. A detailed investigation of the Fc-CHAP-LSN mode of action revealed that upon binding to the bacterial cell, but not in solution, LSN mediates its own release by cleaving the Gly-Gly CHAP-LSN linker. The bactericidal activity of Fc-CHAP-LSN is driven by the LSN-catalyzed and target cell-dependent release of free LSN. The half-life extended lysin acts as a pro-drug, unveiling a novel mechanism of targeted release and an alternative approach to half-life extension.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2026.1880134","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T21:25:13Z","timestamp":1787347513000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A chimeric, half-life extended lysin with a unique mode of action"],"prefix":"10.3389","volume":"17","author":[{"given":"Zehra","family":"Visram","sequence":"first","affiliation":[{"name":"BioNTech R&D Austria","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donaat","family":"Kestemont","sequence":"additional","affiliation":[{"name":"BioNTech R&D Austria","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Bauer","sequence":"additional","affiliation":[{"name":"BioNTech R&D Austria","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renping","family":"Qiao","sequence":"additional","affiliation":[{"name":"BioNTech R&D Austria","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Durica-Mitic","sequence":"additional","affiliation":[{"name":"BioNTech R&D Austria","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Majoros-Hashempour","sequence":"additional","affiliation":[{"name":"BioNTech R&D Austria","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Schmidt","sequence":"additional","affiliation":[{"name":"BioNTech R&D Austria","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo","family":"Berdaguer","sequence":"additional","affiliation":[{"name":"BioNTech R&D Austria","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Krey","sequence":"additional","affiliation":[{"name":"BioNTech R&D Austria","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Mutti","sequence":"additional","affiliation":[{"name":"BioNTech R&D Austria","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Zerbs","sequence":"additional","affiliation":[{"name":"BioNTech R&D Austria","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"von Freyberg","sequence":"additional","affiliation":[{"name":"BioNTech R&D Austria","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Corsini","sequence":"additional","affiliation":[{"name":"BioNTech R&D Austria","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Badarau","sequence":"additional","affiliation":[{"name":"BioNTech R&D Austria","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"antibiotics14121285","DOI":"10.3390\/antibiotics14121285","article-title":"Recent advances in Endolysin engineering","volume":"14","author":"Aitken","year":"2025","journal-title":"Antibiotics (Basel)"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"eLife.93673","DOI":"10.7554\/eLife.93673","article-title":"Reassessing the substrate specificities of the major Staphylococcus aureus peptidoglycan hydrolases lysostaphin and LytM","volume":"13","author":"Antenucci","year":"2024","journal-title":"eLife"},{"key":"ref3","doi-asserted-by":"crossref","DOI":"10.64898\/2026.04.27.720530","article-title":"Multi-dimensional optimization of a lysin towards a ribolysin against life-threatening S. aureus infections: fc-LysM-CHAP and its strong synergy with standard of care antibiotics","volume-title":"bioRxiv","author":"Badarau","year":"2026"},{"key":"ref4","first-page":"123","article-title":"All Staphylococcus aureus bacteraemia-inducing strains can cause infective endocarditis: results of GWAS and experimental animal studies","volume-title":"J. 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