{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T03:20:57Z","timestamp":1784604057122,"version":"3.55.0"},"reference-count":74,"publisher":"National Academy of Sciences","issue":"49","license":[{"start":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T00:00:00Z","timestamp":1669680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012415","name":"A*STAR | Biomedical Research Council","doi-asserted-by":"publisher","award":["EDB IAF-PP grant (H17\/01\/a0\/004)"],"award-info":[{"award-number":["EDB IAF-PP grant (H17\/01\/a0\/004)"]}],"id":[{"id":"10.13039\/501100012415","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012415","name":"A*STAR | Biomedical Research Council","doi-asserted-by":"publisher","award":["IAF-PP (HBMS) grant Asian Skin Microbiome Program IAF-PP grant (H18\/01a0\/016)"],"award-info":[{"award-number":["IAF-PP (HBMS) grant Asian Skin Microbiome Program IAF-PP grant (H18\/01a0\/016)"]}],"id":[{"id":"10.13039\/501100012415","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001459","name":"Ministry of Education - Singapore","doi-asserted-by":"publisher","award":["AcRF Tier 1 grant (R-143-000-B79-114 and R-143-000-C16-114)"],"award-info":[{"award-number":["AcRF Tier 1 grant (R-143-000-B79-114 and R-143-000-C16-114)"]}],"id":[{"id":"10.13039\/501100001459","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001350","name":"Ministry of Health -Singapore","doi-asserted-by":"publisher","award":["National Medical Research Council (MOH-000612-00)"],"award-info":[{"award-number":["National Medical Research Council (MOH-000612-00)"]}],"id":[{"id":"10.13039\/501100001350","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science foundation","doi-asserted-by":"crossref","award":["310030_189255"],"award-info":[{"award-number":["310030_189255"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,12,6]]},"abstract":"<jats:p>\n                    <jats:italic>Malassezia<\/jats:italic>\n                    form the dominant eukaryotic microbial community on the human skin. The\n                    <jats:italic>Malassezia<\/jats:italic>\n                    genus possesses a repertoire of secretory hydrolytic enzymes involved in protein and lipid metabolism which alter the external cutaneous environment. The exact role of most\n                    <jats:italic>Malassezia<\/jats:italic>\n                    secreted enzymes, including those in interaction with the epithelial surface, is not well characterized. In this study, we compared the expression level of secreted proteases, lipases, phospholipases, and sphingomyelinases of\n                    <jats:italic>Malassezia globosa<\/jats:italic>\n                    in healthy subjects and seborrheic dermatitis or atopic dermatitis patients. We observed upregulated gene expression of the previously characterized secretory aspartyl protease\n                    <jats:italic>MGSAP1<\/jats:italic>\n                    in both diseased groups, in lesional and non-lesional skin sites, as compared to healthy subjects. To explore the functional roles of\n                    <jats:italic>MGSAP1<\/jats:italic>\n                    in skin disease, we generated a knockout mutant of the homologous protease\n                    <jats:italic>MFSAP1<\/jats:italic>\n                    in the genetically tractable\n                    <jats:italic>Malassezia furfur<\/jats:italic>\n                    . We observed the loss of\n                    <jats:italic>MFSAP1<\/jats:italic>\n                    resulted in dramatic changes in the cell adhesion and dispersal in both culture and a human 3D reconstituted epidermis model. In a murine model of\n                    <jats:italic>Malassezia<\/jats:italic>\n                    colonization, we further demonstrated Mfsap1 contributes to inflammation as observed by reduced edema and inflammatory cell infiltration with the knockout mutant versus wildtype. Taken together, we show that this dominant secretory\n                    <jats:italic>Malassezia<\/jats:italic>\n                    aspartyl protease has an important role in enabling a planktonic cellular state that can potentially aid in colonization and additionally as a virulence factor in barrier-compromised skin, further highlighting the importance of considering the contextual relevance when evaluating the functions of secreted microbial enzymes.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2212533119","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T17:14:31Z","timestamp":1669655671000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":43,"title":["The human pathobiont\n                    <i>Malassezia furfur<\/i>\n                    secreted protease Mfsap1 regulates cell dispersal and exacerbates skin inflammation"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3378-0117","authenticated-orcid":false,"given":"Joleen P. Z.","family":"Goh","sequence":"first","affiliation":[{"name":"A*STAR Skin Research Labs, Agency for Science, Technology and Research, Singapore 138648"},{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore 308232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiorella","family":"Ruchti","sequence":"additional","affiliation":[{"name":"Section of Immunology, Vetsuisse Faculty and Institute of Experimental Immunology, University of Z\u00fcrich, Z\u00fcrich CH-8057, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4990-4820","authenticated-orcid":false,"given":"Si En","family":"Poh","sequence":"additional","affiliation":[{"name":"Molecular Engineering Lab, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winston L. C.","family":"Koh","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering and Bioimaging, Agency for Science, Technology and Research, Singapore 138669"},{"name":"Bioinformatics Institute, Agency for Science, Technology and Research, Singapore 138671"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2139-3304","authenticated-orcid":false,"given":"Kiat Yi","family":"Tan","sequence":"additional","affiliation":[{"name":"Functional Proteomics Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan Ting","family":"Lim","sequence":"additional","affiliation":[{"name":"Functional Proteomics Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven T. G.","family":"Thng","sequence":"additional","affiliation":[{"name":"National Skin Centre, National Healthcare Group, Singapore 308205"},{"name":"Skin Research Institute of Singapore, Agency for Science, Technology and Research, Singapore 308232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2455-2526","authenticated-orcid":false,"given":"Radoslaw M.","family":"Sobota","sequence":"additional","affiliation":[{"name":"Functional Proteomics Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn S.","family":"Hoon","sequence":"additional","affiliation":[{"name":"Molecular Engineering Lab, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxi","family":"Liu","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093-0657"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5695-0409","authenticated-orcid":false,"given":"Anthony J.","family":"O\u2019Donoghue","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093-0657"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5724-4837","authenticated-orcid":false,"given":"Salom\u00e9","family":"LeibundGut-Landmann","sequence":"additional","affiliation":[{"name":"Section of Immunology, Vetsuisse Faculty and Institute of Experimental Immunology, University of Z\u00fcrich, Z\u00fcrich CH-8057, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7607-3124","authenticated-orcid":false,"given":"Hazel H.","family":"Oon","sequence":"additional","affiliation":[{"name":"National Skin Centre, National Healthcare Group, Singapore 308205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6652-4793","authenticated-orcid":false,"given":"Hao","family":"Li","sequence":"additional","affiliation":[{"name":"Molecular Engineering Lab, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673"},{"name":"Department of Chemistry, National University of Singapore, Singapore 117543"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3878-1722","authenticated-orcid":false,"suffix":"Jr.","given":"Thomas L.","family":"Dawson","sequence":"additional","affiliation":[{"name":"A*STAR Skin Research Labs, Agency for Science, Technology and Research, Singapore 138648"},{"name":"Skin Research Institute of Singapore, Agency for Science, Technology and Research, Singapore 308232"},{"name":"Department of Drug Discovery, School of Pharmacy, Medical University of South Carolina, Charleston, SC 29425"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,11,29]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2013.10.001"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2537"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2019.02.010"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00021-11"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/mmy\/myx134"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2019.01.007"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1608-2"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-021-01011-w"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.614446"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.01891"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.00370"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2003.12.034"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/ANC.0000000000000640"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1708580114"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1159\/000181144"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature25177"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.00397-21","article-title":"Secretory proteases of the human skin microbiome","volume":"90","author":"Chua W.","year":"2021","unstructured":"W. Chua, S. E. Poh, H. Li, Secretory proteases of the human skin microbiome. Infect. Immun. 90, e0039721 (2021).","journal-title":"Infect. Immun."},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1078\/1438-4221-00223"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.67.3.400-428.2003"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.03081"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2003.12.034"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002701"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm4061217"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00572-12"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.15.4.545-563.2002"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.5021\/ad.2016.28.6.733"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00338-17"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2017.10.024"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-30588-2"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.62.3.597-635.1998"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2017.11.034"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.00148"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1323732111"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2182"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.TIR118.001099"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006051"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01514-16"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1080\/13693780701225767"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/mmy\/myw002"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2018.05.003"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/mmy\/myx014"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1984.tb00743.x"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.132"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2019.02.002"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.00367"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1087-0024.2005.10119.x"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0706756104"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700844"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2011.10573.x"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/ics.12055"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2017.10.024"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2001.117849"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-015-0567-4"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.53944"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.riam.2015.10.003"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11046-010-9386-2"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fgb.2013.08.005"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.01608"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1080\/mmy.38.3.239.247"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.3109\/13693786.2012.678019"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c02177"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.3109\/09546634.2012.687089"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.209601.116"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01853-16"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.153.1.163-168.1983"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.2144\/05381BM04"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.1c00138"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth1109-786"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005614"},{"key":"e_1_3_4_72_2","volume-title":"The Principles of Humane Experimental Technique","author":"Russell W. M. S.","year":"1959","unstructured":"W. M. S. Russell, R. L. Burch, The Principles of Humane Experimental Technique, (AMPCo, 1959)."},{"key":"e_1_3_4_73_2","first-page":"60175","article-title":"Infecting mice with Malassezia spp. to study the fungus-host interaction","volume":"2019","author":"Sparber F.","year":"2019","unstructured":"F. Sparber, S. LeibundGut-Landmann, Infecting mice with Malassezia spp. to study the fungus-host interaction. J. Vis. Exp. 2019, 60175 (2019).","journal-title":"J. Vis. Exp."},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201646632"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2212533119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T08:39:05Z","timestamp":1695285545000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2212533119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,29]]},"references-count":74,"journal-issue":{"issue":"49","published-print":{"date-parts":[[2022,12,6]]}},"alternative-id":["10.1073\/pnas.2212533119"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2212533119","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,29]]},"assertion":[{"value":"2022-07-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2212533119"}}