Document Type

Article

Publication Date

2026

DOI

10.1186/s12866-026-05405-w

Publication Title

BMC Microbiology

Volume

Advance online publication

Pages

27 pp.

Abstract

Background

Accurate interpretation of Candida detection in women with vulvovaginal symptoms remains difficult, because organism recovery may reflect either clinically relevant infection or nonpathogenic colonization. We have recently demonstrated that the secreted fungal zinc-binding protein, Pra1 is responsible for driving the inflammatory immunopathology of VVC. We therefore reasoned that PRA1 expression by Candida albicans in the vagina may act as a diagnostic tool to discriminate between commensal colonisation and active disease.

Methods

We conducted a 12-week prospective, single-center exploratory biomarker analysis nested within a registered parent clinical trial. Nine women with vulvovaginal symptoms provided cervicovaginal lavage samples and clinical data at baseline and at weeks 4, 8, and 12. This report does not present the primary efficacy analysis of the randomized trial. At each visit, Candida culture status and clinical severity score (CSS) were recorded. Symptomatic Candida vaginitis was defined as Candida culture positivity with CSS ≥ 3 at the same visit. Species identification of fungal isolates was performed by MALDI-TOF mass spectrometry, and vaginal PRA1 was quantified by SYBR Green real-time qPCR. Vaginal PRA1 concentrations were assessed as a time-varying same-visit biomarker using repeated-measures approaches, non-parametric comparisons, correlation analyses, and receiver operating characteristic (ROC) curves.

Results

PRA1 concentrations were substantially higher in Candida culture-positive than in culture-negative samples (median 4,011 vs. 21.5 pg/µL, p = 3.99 × 10⁻⁵). PRA1 was also higher in samples meeting criteria for symptomatic Candida vaginitis than in asymptomatic culture-negative samples (median 11,762 vs. 21.5 pg/µL, p = 8.15 × 10⁻⁵). Among culture-positive observations, PRA1 was associated with symptom severity (Spearman rho = 0.67; Pearson r = 0.56 after log10 transformation). Same-visit discrimination was high in this cohort for both Candida culture positivity and symptomatic Candida vaginitis (AUC approximately 0.95 for each outcome). In this small exploratory cohort, lower PRA1 thresholds achieved 100% sensitivity and negative predictive value for clinically significant Candida vaginitis. These estimates require validation in larger studies.

Conclusions

These preliminary findings suggest that vaginal PRA1 may help distinguish symptomatic Candida-associated disease from clinically insignificant Candida detection and may be particularly useful as a rule-out biomarker. Given the small sample size and exploratory design, these results should be regarded as hypothesis-generating and require validation in larger, independent cohorts.

Rights

© 2026 The Authors.

This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original authors and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

Data Availability

Article states: "The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request."

Original Publication Citation

Roselletti, E., Kozma, B., Ratonyi, D., Kunkli, A., Kozma, B., Takacs, P., & Wilson, D. (2026). Vaginal PRA1 identifies clinically relevant Candida albicans vaginitis and excludes asymptomatic colonization: An exploratory study. BMC Microbiology. Advance online publication. https://doi.org/10.1186/s12866-026-05405-w

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Supplementary Information

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