# Oral Epithelial Cells, Candida and PMN Activation

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2022 · $564,656

## Abstract

PROJECT SUMMARY
The oral mucosal microbiota is a complex ecosystem primarily represented by bacteria and fungi. Most
oropharyngeal fungal infections are caused by the genus Candida and are assumed to result from an
overgrowth of indigenous species, primarily C. albicans. C. albicans is a commensal colonizer of the oral
mucosa in humans, but is also responsible for infections afflicting immunocompromised hosts. Persistent
oropharyngeal thrush is refractory to most antifungals and a significant clinical problem in pharmacologically
immunosuppressed patients. Corticosteroid-induced and chemotherapy-induced immunosuppression, are two
main risk factors for oropharyngeal candidiasis in humans. C. albicans also causes fungemia, a serious
consequence of cancer cytotoxic chemotherapy, which is thought to develop from fungal translocation through
compromised mucosal barriers. Changes in endogenous bacterial population size or composition and in the
host environment can transform fungal commensals into pathobionts. Work in our previous funding cycle
established a synergistic relationship of mitis group streptococci with C. albicans in the pathogenesis of oral
candidiasis. We identified mechanisms of synergy which involved both a direct effect on fungal virulence gene
expression and a modification of host responses. In this project we will build on our ongoing studies examining
the interplay of the resident oral mucosal bacterial microbiota and C. albicans. We will use mouse models of
commensal colonization or mucosal infection to interrogate oral bacterial microbiome parameters that promote
C. albicans virulence. In aim 1 we will characterize dysbiotic changes in mucosa-associated bacterial
communities in oropharyngeal candidiasis, using our established mouse models of cortisone- and
chemotherapy-induced immunosuppression. We will then test the hypothesis that certain endogenous bacterial
species isolated from dysbiotic states can exhibit pathogenic synergy with C. albicans. In aim 2 we will define
the regulatory mechanisms of fungal-bacterial mucosal biofilm growth in each immunosuppression state.
Finally, in aim 3 we will examine the role of the dysbiotic communities and host response in mucosal barrier
breach and bloodstream dissemination by C. albicans. The proposed studies have the potential to lead to a
paradigm shift in how clinicians and scientists view the microbiome changes characterizing mucosal Candida
infections. This project will identify certain oral bacteria as new, clinically relevant mediators of invasive fungal
infections thus providing justification for the combined use of antifungal and anti-bacterial treatments in at risk
patients. A better understanding of the relationship between fungi and the oral microbiome could also result in
new biomarkers of infection risk or identification of probiotic commensals that could lower the likelihood of
invasive mucosal candidiasis in high-risk populations such as patients undergoing intensive cance...

## Key facts

- **NIH application ID:** 10451819
- **Project number:** 5R01DE013986-18
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Anna I Dongari-Bagtzoglou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $564,656
- **Award type:** 5
- **Project period:** 2000-09-29 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10451819

## Citation

> US National Institutes of Health, RePORTER application 10451819, Oral Epithelial Cells, Candida and PMN Activation (5R01DE013986-18). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10451819. Licensed CC0.

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