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dc.contributor.authorRoselletti, E
dc.contributor.authorPericolini, E
dc.contributor.authorNore, A
dc.contributor.authorTakacs, P
dc.contributor.authorKozma, B
dc.contributor.authorSala, A
dc.contributor.authorDe Seta, F
dc.contributor.authorComar, M
dc.contributor.authorUsher, J
dc.contributor.authorBrown, GD
dc.contributor.authorWilson, D
dc.date.accessioned2023-12-12T13:49:52Z
dc.date.issued2023-12-06
dc.date.updated2023-12-12T12:26:46Z
dc.description.abstractCandida causes an estimated half-billion cases of vulvovaginal candidiasis (VVC) every year. VVC is most commonly caused by Candida albicans, which, in this setting, triggers nonprotective neutrophil infiltration, aggressive local inflammation, and symptomatic disease. Despite its prevalence, little is known about the molecular mechanisms underpinning the immunopathology of this fungal infection. In this study, we describe the molecular determinant of VVC immunopathology and a potentially straightforward way to prevent disease. In response to zinc limitation, C. albicans releases a trace mineral binding molecule called Pra1 (pH-regulated antigen). Here, we show that the PRA1 gene is strongly up-regulated during vaginal infections and that its expression positively correlated with proinflammatory cytokine concentrations in women. Genetic deletion of PRA1 prevented vaginal inflammation in mice, and application of a zinc solution down-regulated expression of the gene and also blocked immunopathology. We also show that treatment of women suffering from recurrent VVC with a zinc gel prevented reinfections. We have therefore identified a key mediator of symptomatic VVC, giving us an opportunity to develop a range of preventative measures for combatting this disease.en_GB
dc.description.sponsorshipWellcome Trusten_GB
dc.description.sponsorshipMedical Research Council (MRC)en_GB
dc.description.sponsorshipNational Institute for Health and Care Research (NIHR)en_GB
dc.description.sponsorshipBiotechnology and Biological Sciences Research Council (BBSRC)en_GB
dc.identifier.citationVol. 15(725), article eadi3363en_GB
dc.identifier.doihttps://doi.org/10.1126/scitranslmed.adi3363
dc.identifier.grantnumber214317/Z/18/Zen_GB
dc.identifier.grantnumberMR/N006364/2en_GB
dc.identifier.grantnumberMR/V033417/1en_GB
dc.identifier.grantnumberBB/W009625/1en_GB
dc.identifier.urihttp://hdl.handle.net/10871/134775
dc.identifierORCID: 0000-0003-3929-7502 (Roselletti, Elena)
dc.identifierORCID: 0000-0002-0604-291X (Usher, Jane)
dc.identifierORCID: 0000-0002-0287-5383 (Brown, Gordon D)
dc.identifierORCID: 0000-0001-6617-0123 (Wilson, Duncan)
dc.language.isoenen_GB
dc.publisherAmerican Association for the Advancement of Science (AAAS)en_GB
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pubmed/38055800en_GB
dc.rights© 2023 The Authors; exclusive licensee American Association for the Advancement of Science. This version is made available under the CC-BY 4.0 license: https://creativecommons.org/licenses/by/4.0/  en_GB
dc.titleZinc prevents vaginal candidiasis by inhibiting expression of an inflammatory fungal proteinen_GB
dc.typeArticleen_GB
dc.date.available2023-12-12T13:49:52Z
dc.identifier.issn1946-6234
exeter.place-of-publicationUnited States
dc.descriptionThis is the author accepted manuscript. The final version is available from the American Association for the Advancement of Science via the DOI in this recorden_GB
dc.descriptionData and materials availability: All data associated with this study are present in the paper or the Supplementary Materials. Raw data from the figures are given in data file S1.en_GB
dc.identifier.eissn1946-6242
dc.identifier.journalScience Translational Medicineen_GB
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_GB
dcterms.dateAccepted2023-11-15
rioxxterms.versionAMen_GB
rioxxterms.licenseref.startdate2023-12-06
rioxxterms.typeJournal Article/Reviewen_GB
refterms.dateFCD2023-12-12T13:45:20Z
refterms.versionFCDAM
refterms.dateFOA2023-12-12T13:50:17Z
refterms.panelAen_GB
refterms.dateFirstOnline2023-12-06


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© 2023 The Authors; exclusive licensee American Association for the Advancement of Science. This version is made available under the CC-BY 4.0 license: https://creativecommons.org/licenses/by/4.0/  
Except where otherwise noted, this item's licence is described as © 2023 The Authors; exclusive licensee American Association for the Advancement of Science. This version is made available under the CC-BY 4.0 license: https://creativecommons.org/licenses/by/4.0/