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In contrast to <jats:italic>C. albicans<\/jats:italic>, which produces secreted aspartic proteases (Saps) involved in pathogenicity, <jats:italic>C. glabrata<\/jats:italic> expresses a distinct group of cell surface-associated aspartic proteases known as yapsins (Yps). While <jats:italic>YPS<\/jats:italic> gene deletion mutants have proposed roles in cellular homeostasis, their precise contribution to fungal virulence and host interactions remains unclear. Herein, we present the first detailed biochemical and functional characterization of two native Yps proteins, Yps3 and Yps9, purified from <jats:italic>C. glabrata<\/jats:italic> cultures. Both proteases displayed robust activity in a mildly acidic to neutral pH range (5.5\u20137.0), resistance to the classical aspartic protease inhibitor pepstatin A, and selectively degraded key host antimicrobial peptides, including LL-37 cathelicidin, histatin 5 (Hst5), and kininogen-derived peptide NAT26, by hydrolyzing lysine residues. Additionally, Yps9 promoted <jats:italic>C. albicans<\/jats:italic> biofilm dispersal. In a <jats:italic>Galleria mellonella<\/jats:italic> infection model, a pre-treatment with each protease enhanced larval survival and increased phenol oxidase activity, implying a role of yapsins in immune priming. Collectively, these findings reveal multifunctional roles for Yps3 and Yps9 in fungal virulence, biofilm modulation, and host immune interactions.<\/jats:p>","DOI":"10.1038\/s41598-025-15577-6","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T09:44:39Z","timestamp":1756719879000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Functional roles of purified yapsins from Candida glabrata (Nakaseomyces glabratus) in immune modulation and cross-species biofilm formation"],"prefix":"10.1038","volume":"15","author":[{"given":"Dorota","family":"Satala","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"Satala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamila","family":"Kulig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justyna","family":"Karkowska-Kuleta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Kozik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Rapala-Kozik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,1]]},"reference":[{"key":"15577_CR1","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1016\/j.resmic.2009.08.017","volume":"160","author":"H Ingmer","year":"2009","unstructured":"Ingmer, H. & Br\u00f8ndsted, L. 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