{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T11:35:52Z","timestamp":1784806552502,"version":"3.55.0"},"reference-count":32,"publisher":"Portland Press Ltd.","issue":"01","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001348","name":"Agency for Science, Technology and Research","doi-asserted-by":"crossref","award":["H18\/01\/a0\/016"],"award-info":[{"award-number":["H18\/01\/a0\/016"]}],"id":[{"id":"10.13039\/501100001348","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001350","name":"Ministry of Health -Singapore","doi-asserted-by":"crossref","award":["MOH-000612-00"],"award-info":[{"award-number":["MOH-000612-00"]}],"id":[{"id":"10.13039\/501100001350","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,1,7]]},"abstract":"<jats:p>Malassezia is the dominant genus of fungi residing on human skin and is associated with both healthy skin and many dermatological conditions. Among these skin diseases, pityriasis versicolor (PV) has strong etiological connections with Malassezia. In the hyper- or hypo-pigmented scales of PV patients, Malassezia is enriched in its mycelial form, which is rarely present on healthy skin. How these Malassezia hyphae contribute to disease pathology in PV is unknown. In this study, we observed a distinct shift in the extracellular proteolytic activity when Malassezia furfur transitions from yeast to hyphae. We identified that the expression of the aspartyl protease MfSAP2 is dramatically up-regulated at both the mRNA and protein level when M. furfur is in the mycelial form. We determined the protease substrate specificity and observed that MfSAP2 can degrade corneodesmosome proteins, which are intercellular adhesive proteins between corneocytes in the stratum corneum. In a 3D human skin model with MfSAP2 treatment, we observed clear degradation of corneodesmosin, a component of the corneodesmosome. Taken together, our study demonstrates that a secreted protease is a key virulence factor associated with M. furfur mycelium and is potentially involved in the disease pathogenesis of PV.<\/jats:p>","DOI":"10.1042\/bcj20253109","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T07:44:15Z","timestamp":1764747855000},"page":"23-36","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Aspartyl protease MfSAP2 is a key virulence factor in mycelial form of skin fungi\n                    <i>Malassezia furfur<\/i>"],"prefix":"10.1042","volume":"483","author":[{"given":"Wisely","family":"Chua","sequence":"first","affiliation":[{"name":"1Molecular Engineering Lab, Institute of Molecular and Cell Biology, Agency for Science Technology and Research, 138673, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Hei","sequence":"additional","affiliation":[{"name":"2Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li Fang","family":"Koh","sequence":"additional","affiliation":[{"name":"3A*STAR Skin Research Labs (A*SRL), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, 138648Singapore"},{"name":"4Skin Research Institute of Singapore (SRIS), 8A Biomedical Grove, 138648, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belle Lin Hwee","family":"Yap","sequence":"additional","affiliation":[{"name":"3A*STAR Skin Research Labs (A*SRL), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, 138648Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Ling","family":"Saw","sequence":"additional","affiliation":[{"name":"1Molecular Engineering Lab, Institute of Molecular and Cell Biology, Agency for Science Technology and Research, 138673, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tha\u00eds Helena","family":"Maciel Fernandes","sequence":"additional","affiliation":[{"name":"5Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, 92093, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elany Barbosa","family":"da Silva","sequence":"additional","affiliation":[{"name":"5Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, 92093, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirlyn","family":"Goh","sequence":"additional","affiliation":[{"name":"1Molecular Engineering Lab, Institute of Molecular and Cell Biology, Agency for Science Technology and Research, 138673, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas L.","family":"Dawson","sequence":"additional","affiliation":[{"name":"3A*STAR Skin Research Labs (A*SRL), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, 138648Singapore"},{"name":"4Skin Research Institute of Singapore (SRIS), 8A Biomedical Grove, 138648, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"O\u2019Donoghue","sequence":"additional","affiliation":[{"name":"5Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, 92093, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3280-7365","authenticated-orcid":false,"given":"John E.","family":"Common","sequence":"additional","affiliation":[{"name":"3A*STAR Skin Research Labs (A*SRL), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, 138648Singapore"},{"name":"4Skin Research Institute of Singapore (SRIS), 8A Biomedical Grove, 138648, Singapore"},{"name":"6Translational and Clinical Research Institute and NIHR Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6652-4793","authenticated-orcid":false,"given":"Hao","family":"Li","sequence":"additional","affiliation":[{"name":"1Molecular Engineering Lab, Institute of Molecular and Cell Biology, Agency for Science Technology and Research, 138673, Singapore"},{"name":"3A*STAR Skin Research Labs (A*SRL), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, 138648Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"2026010812025982800_BCJ-2025-3109C1","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/nature12171","article-title":"Topographic diversity of fungal and bacterial communities in human skin","volume":"498","author":"Findley","year":"2013","journal-title":"Nature"},{"key":"2026010812025982800_BCJ-2025-3109C2","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.mib.2017.10.024","article-title":"Host-microbe interactions: Malassezia and human skin","volume":"40","author":"Grice","year":"2017","journal-title":"Curr. 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