# Carbon Regulation of Virulence in Oropharyngeal Candidiasis

> **NIH NIH R21** · UNIVERSITY OF GEORGIA · 2020 · $207,323

## Abstract

Candida albicans is a frequent causative agent of oropharyngeal candidiasis (OPC), an infection of the oral
mucosa. OPC causes significant morbidity among patients with diverse risk factors, including dentures,
diabetes, cancer, HIV/AIDS, use of antibiotics or corticosteroids, dry mouth, and smoking. There is no
surveillance for these infections in the US, but worldwide estimates indicate that HIV/AIDS patients alone
present 10 million cases of OPC annually. Clinical practice guidelines recommend azole antifungal treatment
for OPC. However, azole resistance continues to emerge, in particular after repeated exposure, and it is thus
critical to develop new strategies to prevent and treat OPC.
 The C. albicans genes and pathways that govern pathogenicity in OPC have not been extensively
characterized. Only 14 C. albicans genes are known to be required for virulence in the mouse model of OPC.
We have used RNA-seq expression profiling of C. albicans in a mouse OPC infection model to identify
candidate virulence determinants. Infecting C. albicans cells expressed high RNA levels for genes that enable
alternative (i.e., non-glucose) carbon source utilization. This observation suggests that C. albicans cells
proliferate on alternative carbon sources during OPC.
 We have found that two C. albicans transcription factors, Mig1 and Mig2, function redundantly to shut
off alternative carbon utilization genes. Our data suggest that effects of Mig1 and Mig2 may be mediated in
part by two transcriptional activators of alternative carbon utilization genes, Adr1 and Try4. Both ADR1 and
TRY4 RNAs are greatly up-regulated in C. albicans cells in the OPC model, compared to cells grown in RPMI.
These results led us to the hypothesis that Adr1 and Try4 are required to activate alternative carbon utilization
genes in infecting C. albicans cells during OPC, enabling their proliferation and, ultimately, OPC pathogenesis.
We seek to define functional relationships among alternative carbon utilization genes, their regulators, and
OPC pathogenesis through definition of the regulatory circuitry that governs alternative carbon utilization genes
downstream of Mig1 and Mig2, and through definition of the impact of defects in carbon utilization and its
regulation on OPC.
 Carbon utilization has been studied in the context of invasive candidiasis and gut colonization. To our
knowledge, though, there have been no functional studies of carbon utilization in OPC. The results of our
analysis will uncover basic aspects of C. albicans biology during OPC. This information will likely be applicable
to other mucosal infections, such as vulvovaginal candidiasis, and holds promise to identify novel targets for
antifungal agents.

## Key facts

- **NIH application ID:** 10135300
- **Project number:** 7R21AI144878-02
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** AARON P MITCHELL
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $207,323
- **Award type:** 7
- **Project period:** 2019-02-04 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135300

## Citation

> US National Institutes of Health, RePORTER application 10135300, Carbon Regulation of Virulence in Oropharyngeal Candidiasis (7R21AI144878-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10135300. Licensed CC0.

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