{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:57:39Z","timestamp":1793318259336,"version":"4.5.0"},"reference-count":31,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"725","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2023,12,6]]},"abstract":"<jats:p>\n                    <jats:italic>Candida<\/jats:italic>\n                    causes an estimated half-billion cases of vulvovaginal candidiasis (VVC) every year. VVC is most commonly caused by\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    , 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,\n                    <jats:italic>C. albicans<\/jats:italic>\n                    releases a trace mineral binding molecule called Pra1 (pH-regulated antigen). Here, we show that the\n                    <jats:italic>PRA1<\/jats:italic>\n                    gene is strongly up-regulated during vaginal infections and that its expression positively correlated with proinflammatory cytokine concentrations in women. Genetic deletion of\n                    <jats:italic>PRA1<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adi3363","type":"journal-article","created":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T13:59:15Z","timestamp":1701871155000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":67,"title":["Zinc prevents vaginal candidiasis by inhibiting expression of an inflammatory fungal protein"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3929-7502","authenticated-orcid":true,"given":"Elena","family":"Roselletti","sequence":"first","affiliation":[{"name":"Medical Research Council Centre for Medical Mycology at the University of Exeter, University of Exeter, Geoffrey Pope Building Stocker Road, Exeter EX4 4QD, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5299-8197","authenticated-orcid":true,"given":"Eva","family":"Pericolini","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia, Modena 41125, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1882-8917","authenticated-orcid":true,"given":"Alexandre","family":"Nore","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Medical Mycology at the University of Exeter, University of Exeter, Geoffrey Pope Building Stocker Road, Exeter EX4 4QD, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0078-5763","authenticated-orcid":true,"given":"Peter","family":"Takacs","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, University of Debrecen, Debrecen 4032, Hungary."},{"name":"Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA 23507, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7341-5942","authenticated-orcid":true,"given":"Bence","family":"Kozma","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, University of Debrecen, Debrecen 4032, Hungary."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0766-7943","authenticated-orcid":true,"given":"Arianna","family":"Sala","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia, Modena 41125, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"De Seta","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery, and Health Sciences, Institute for Maternal and Child Health\u2013IRCCS, Burlo Garofolo, University of Trieste, Trieste 34137, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manola","family":"Comar","sequence":"additional","affiliation":[{"name":"Unit of Advanced Microbiology Diagnosis and Translational Research, Institute for Maternal and Child Health\u2013IRCCS, Burlo Garofolo, University of Trieste, Trieste 34137, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0604-291X","authenticated-orcid":true,"given":"Jane","family":"Usher","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Medical Mycology at the University of Exeter, University of Exeter, Geoffrey Pope Building Stocker Road, Exeter EX4 4QD, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0287-5383","authenticated-orcid":true,"given":"Gordon D.","family":"Brown","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Medical Mycology at the University of Exeter, University of Exeter, Geoffrey Pope Building Stocker Road, Exeter EX4 4QD, 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