{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T02:21:14Z","timestamp":1774664474523,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pgen.1010405","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T00:00:00Z","timestamp":1664409600000}}],"reference-count":80,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T00:00:00Z","timestamp":1663545600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R01AI53599-01"],"award-info":[{"award-number":["1R01AI53599-01"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R15AI144683-01"],"award-info":[{"award-number":["1R15AI144683-01"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    In order to successfully induce disease, the fungal pathogen\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    regulates exposure of antigens like the cell wall polysaccharide \u00df(1,3)-glucan to the host immune system.\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>albicans<\/jats:italic>\n                    covers (masks) \u00df(1,3)-glucan with a layer of mannosylated glycoproteins, which aids in immune system evasion by acting as a barrier to recognition by host pattern recognition receptors. Consequently, enhanced \u00df(1,3)-glucan exposure (unmasking) makes fungal cells more visible to host immune cells and facilitates more robust fungal clearance. However, an understanding of how\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>albicans<\/jats:italic>\n                    regulates its exposure levels of \u00df(1,3)-glucan is needed to leverage this phenotype. Signal transduction pathways and their corresponding effector genes mediating these changes are only beginning to be defined. Here, we report that the phosphatase calcineurin mediates unmasking of \u00df(1,3)-glucan in response to inputs from the Cek1 MAPK pathway and in response to caspofungin exposure. In contrast, calcineurin reduces \u00df-glucan exposure in response to high levels of extracellular calcium. Thus, depending on the input, calcineurin acts as a switchboard to regulate \u00df(1,3)-glucan exposure levels. By leveraging these differential \u00df(1,3)-glucan exposure phenotypes, we identified two novel effector genes in the calcineurin regulon,\n                    <jats:italic>FGR41<\/jats:italic>\n                    and\n                    <jats:italic>C1_11990W_A<\/jats:italic>\n                    , that encode putative cell wall proteins and mediate masking\/unmasking. Loss of either effector caused unmasking and attenuated virulence during systemic infection in mice. Furthermore, immunosuppression restored the colonization decrease seen in mice infected with the\n                    <jats:italic>fgr41\u0394\/\u0394<\/jats:italic>\n                    mutant to wild-type levels, demonstrating a reliance on the host immune system for virulence attenuation. Thus, calcineurin and its downstream regulon are general regulators of unmasking.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1010405","type":"journal-article","created":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T13:39:51Z","timestamp":1663594791000},"page":"e1010405","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Cek1 regulates \u00df(1,3)-glucan exposure through calcineurin effectors in Candida albicans"],"prefix":"10.1371","volume":"18","author":[{"given":"Andrew S.","family":"Wagner","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen W.","family":"Lumsdaine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikayla M.","family":"Mangrum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ainsley E.","family":"King","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trevor J.","family":"Hancock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5543-6691","authenticated-orcid":true,"given":"Timothy E.","family":"Sparer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2867-7182","authenticated-orcid":true,"given":"Todd B.","family":"Reynolds","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,9,19]]},"reference":[{"issue":"8","key":"pgen.1010405.ref001","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nrmicro2836","article-title":"Nutritional immunity: transition metals at the pathogen-host interface","volume":"10","author":"MI Hood","year":"2012","journal-title":"Nat Rev Microbiol"},{"key":"pgen.1010405.ref002","first-page":"15","article-title":"Essential metals at the host-pathogen interface: nutritional immunity and micronutrient assimilation by human fungal pathogens","author":"A Crawford","year":"2015","journal-title":"FEMS Yeast Res"},{"issue":"2","key":"pgen.1010405.ref003","doi-asserted-by":"crossref","first-page":"e1006144","DOI":"10.1371\/journal.ppat.1006144","article-title":"A feast for Candida: Metabolic plasticity confers an edge for virulence","volume":"13","author":"P Miramon","year":"2017","journal-title":"PLoS Pathog."},{"issue":"3","key":"pgen.1010405.ref004","doi-asserted-by":"crossref","first-page":"e00055","DOI":"10.1128\/mBio.00055-11","article-title":"The fungal pathogen Candida albicans autoinduces hyphal morphogenesis by raising extracellular pH","volume":"2","author":"S Vylkova","year":"2011","journal-title":"mBio"},{"issue":"2","key":"pgen.1010405.ref005","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1590\/1516-3180.2014.1322640","article-title":"Prevalence of Candida albicans and non-albicans isolates from vaginal secretions: comparative evaluation of colonization, vaginal candidiasis and recurrent vaginal candidiasis in diabetic and non-diabetic women.","volume":"132","author":"LS Gunther","year":"2014","journal-title":"Sao Paulo Med J"},{"issue":"3","key":"pgen.1010405.ref006","first-page":"183","article-title":"Intraluminal pH of the human gastrointestinal tract","volume":"46","author":"J. 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