# Targeted and forward genetic approaches to decipher the pathogenesis of symptomatic vulvovaginal candidiasis

> **NIH NIH R21** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2020 · $228,000

## 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 remains a barrier to progress in better treating and managing this most prevalent human
candidal infection. Despite being associated with vaginitis onset, the role for neutrophils in driving disease
symptoms remain unclear, partly complicated by current animals that do not reflect disease symptomatology.
Guided by strong published and preliminary data, we have now developed a mouse model of infection that results
in classical vaginitis symptoms (redness, swelling, itching of the vaginal mucosa).
Therefore, the objectives of this proposal is to determine if Candidalysin and/or host neutrophils are required
for symptomatic vaginitis and to identify how host genetic variation sensitizes to symptomatic disease. These
aims will test our central hypothesis that Candidalysin is required, while neutrophils are dispensable, for
symptomatic infection. Under the first aim, we will use fungal strains deleted for Candidalysin and neutrophil
depletion strategies to determine requirements of these factors for driving disease symptomatology observed in
DBA/2 mice. The second aim will utilize a reference panel of recombinant inbred mouse strains (BXDs) and
downstream phenotypic and statistical analyses to identify quantitative trait loci (QTLs) associated with
symptomatic infection. Follow up studies using gene expression and knockdown approaches will validate these
findings. The outcomes of this project will provide foundational information regarding the immunopathogenesis
of vulvovaginal candidiasis and may shift the current paradigm of the neutrophil-centric model. We also aim to
identify alleles associated with symptomatic disease that can be interrogated at the human population level in a
future clinical study.

## Key facts

- **NIH application ID:** 9822185
- **Project number:** 5R21AI141829-02
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Brian M Peters
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $228,000
- **Award type:** 5
- **Project period:** 2018-11-13 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9822185

## Citation

> US National Institutes of Health, RePORTER application 9822185, Targeted and forward genetic approaches to decipher the pathogenesis of symptomatic vulvovaginal candidiasis (5R21AI141829-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9822185. Licensed CC0.

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