Zinc prevents vaginal candidiasis by inhibiting expression of an inflammatory fungal protein
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Updated: Jul 9, 2025
Protocols for Vaginal Inoculation and Sample Collection in the Experimental Mouse Model of Candida vaginitis
Published on: December 8, 2011
Elena Roselletti1, Eva Pericolini2, Alexandre Nore1
1Medical Research Council Centre for Medical Mycology at the University of Exeter, University of Exeter, Geoffrey Pope Building Stocker Road, Exeter EX4 4QD, UK.
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.
Insights
Vulvovaginal candidiasis (VVC) is often caused by Candida albicans. Researchers found that the Pra1 protein is a key factor in VVC inflammation and developed a zinc-based treatment to prevent reinfection.
Area of Science:
- Mycology
- Immunology
- Infectious Diseases
Background:
- Vulvovaginal candidiasis (VVC) affects millions annually, primarily caused by Candida albicans.
- The precise molecular mechanisms driving VVC immunopathology remain largely unknown.
- Candida albicans releases Pra1 (pH-regulated antigen) in response to zinc limitation.
Purpose of the Study:
- To identify the molecular determinant of VVC immunopathology.
- To explore a potential preventative strategy for VVC disease.
Main Methods:
- Examined PRA1 gene expression in vaginal infections and correlated it with cytokine levels.
- Utilized genetic deletion of PRA1 in a mouse model of vaginal inflammation.
- Assessed the effect of zinc solution application on PRA1 expression and inflammation.
- Conducted a clinical trial using zinc gel for recurrent VVC prevention.
Main Results:
- PRA1 gene expression was significantly upregulated during vaginal infections and correlated with proinflammatory cytokines.
- Deletion of PRA1 prevented vaginal inflammation in mice.
- Zinc application downregulated PRA1 expression and blocked immunopathology.
- Zinc gel treatment successfully prevented reinfections in women with recurrent VVC.
Conclusions:
- Pra1 is a key mediator of symptomatic VVC immunopathology.
- Targeting Pra1 with zinc offers a promising preventative strategy for VVC.
- This research opens avenues for developing novel VVC preventative measures.
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