Zinc prevents vaginal candidiasis by inhibiting expression of an inflammatory fungal protein
dc.contributor.author | Roselletti, E | |
dc.contributor.author | Pericolini, E | |
dc.contributor.author | Nore, A | |
dc.contributor.author | Takacs, P | |
dc.contributor.author | Kozma, B | |
dc.contributor.author | Sala, A | |
dc.contributor.author | De Seta, F | |
dc.contributor.author | Comar, M | |
dc.contributor.author | Usher, J | |
dc.contributor.author | Brown, GD | |
dc.contributor.author | Wilson, D | |
dc.date.accessioned | 2023-12-12T13:49:52Z | |
dc.date.issued | 2023-12-06 | |
dc.date.updated | 2023-12-12T12:26:46Z | |
dc.description.abstract | Candida 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.sponsorship | Wellcome Trust | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.description.sponsorship | National Institute for Health and Care Research (NIHR) | en_GB |
dc.description.sponsorship | Biotechnology and Biological Sciences Research Council (BBSRC) | en_GB |
dc.identifier.citation | Vol. 15(725), article eadi3363 | en_GB |
dc.identifier.doi | https://doi.org/10.1126/scitranslmed.adi3363 | |
dc.identifier.grantnumber | 214317/Z/18/Z | en_GB |
dc.identifier.grantnumber | MR/N006364/2 | en_GB |
dc.identifier.grantnumber | MR/V033417/1 | en_GB |
dc.identifier.grantnumber | BB/W009625/1 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/134775 | |
dc.identifier | ORCID: 0000-0003-3929-7502 (Roselletti, Elena) | |
dc.identifier | ORCID: 0000-0002-0604-291X (Usher, Jane) | |
dc.identifier | ORCID: 0000-0002-0287-5383 (Brown, Gordon D) | |
dc.identifier | ORCID: 0000-0001-6617-0123 (Wilson, Duncan) | |
dc.language.iso | en | en_GB |
dc.publisher | American Association for the Advancement of Science (AAAS) | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/38055800 | en_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.title | Zinc prevents vaginal candidiasis by inhibiting expression of an inflammatory fungal protein | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2023-12-12T13:49:52Z | |
dc.identifier.issn | 1946-6234 | |
exeter.place-of-publication | United States | |
dc.description | This is the author accepted manuscript. The final version is available from the American Association for the Advancement of Science via the DOI in this record | en_GB |
dc.description | Data 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.eissn | 1946-6242 | |
dc.identifier.journal | Science Translational Medicine | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2023-11-15 | |
rioxxterms.version | AM | en_GB |
rioxxterms.licenseref.startdate | 2023-12-06 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2023-12-12T13:45:20Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2023-12-12T13:50:17Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2023-12-06 |
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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/