# Candidalysin: a key mediator of Candida vaginitis immunopathology

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2020 · $380,000

## Abstract

Candida albicans, the primary causative agent of fungal vaginitis, will affect 75% of all women of reproductive
age at least once in their lifetime. Long believed to result from immunodeficiency, a growing body of evidence
strongly suggests that vaginitis is now considered to be an immunopathology, in which the host response
actually drives disease symptoms. Lack of a comprehensive understanding of the host and fungal factors that
initiate symptomatic disease high remains a barrier to progress in better treating and managing this most
prevalent human fungal infection. Guided by strong preliminary data, we have identified the newly described
fungal toxin Candidalysin as the major virulence factor governing vaginitis pathogenesis.
Therefore, the objective of this proposal is to determine if variation in expression or activity of Candidalysin in
clinical isolates governs C. albicans pathogenicity at the vaginal mucosa. These aims will test our central
hypothesis that variation in Candidalysin activity partly underlies the variable symptomatology of Candida
vaginal colonization and identification of host signaling engaged by Candidalysin may elucidate new molecular
therapeutic targets. Under the first aim, we will determine amino acid residues that contribute to reduced
pathogenicity of a variant Candidalysin observed in clinical isolates. We will also determine differential host
responses to wild-type and variant Candidalysin at the vaginal mucosa. The second aim will focus on
identifying prevalent genetic mechanisms (promoter sequences, Kex proteases) that control Candidalysin
expression and function. We will confirm these by functional level by allelic transfers between strong and weak
Candidalysin expressing strains. The third aim seeks to identify host factors elicited by Candidalysin that may
drive immunopathology in vivo and determine if blockade of these signaling mechanisms can alleviate
symptomatic disease. The outcomes of this project will provide foundational information regarding function of
Candidalysin isoforms, genetic checkpoints of Candidalysin expression, and identify promising new pathways
that may be exploited for the clinical management of vaginitis.

## Key facts

- **NIH application ID:** 9986647
- **Project number:** 5R01AI134796-03
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Brian M Peters
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $380,000
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986647

## Citation

> US National Institutes of Health, RePORTER application 9986647, Candidalysin: a key mediator of Candida vaginitis immunopathology (5R01AI134796-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9986647. Licensed CC0.

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