# Genetic regulation of antifungal drug resistance in Candida albicans

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, MERCED · 2020 · $39,689

## Abstract

PROJECT SUMMARY
Candida albicans is a normal commensal of the human microbiota that is also capable of causing
superficial and disseminated infections in at-risk patient populations. Immunocompromised
individuals and those with head and neck cancers are highly susceptible to Candida infections,
which frequently manifest as oropharyngeal candidiasis. These infections are typically caused by
the formation of a biofilm, a resistant, surface-adhered microbial community that develops on
mucosal surfaces of the mouth or on dental implants within the oral cavity. Formation of a biofilm
provides C. albicans with unique properties, such as increased resistance to antifungal treatments
and the host immune response. It is not uncommon for cells in a biofilm to be several orders of
magnitude more resistant to an antimicrobial agent compared to free-floating cells of the same
species. After treatment of a biofilm-based infection in the oral cavity, persistent surviving cells
can cause treatment failures and permit reinfection of the area. We hypothesize that the antifungal
resistance of C. albicans in the biofilm state is regulated by a complex transcriptional network of
“master” transcriptional regulators and their downstream targets. This proposal aims to discover
the complete transcriptional network controlling resistance mechanisms in C. albicans biofilms. In
Aim 1, we screen a comprehensive library of homozygous transcription factor (TF) deletion
mutants using in vitro biofilm assays to identify regulators with altered growth in the presence of
antifungals commonly prescribed to treat oral C. albicans infections. In Aim 2, we validate our in
vitro findings using an in vivo rat biofilm model of denture stomatitis. In Aim 3, we map the
connections of each transcription factor to one another as well as to downstream target genes to
determine the regulatory network controlling resistance in C. albicans biofilms. This work will
significantly expand our understanding of antifungal resistance mechanisms and may lead to the
development of novel therapeutics against biofilm infections.

## Key facts

- **NIH application ID:** 9976323
- **Project number:** 5F31DE028488-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, MERCED
- **Principal Investigator:** Craig Lewis Ennis
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $39,689
- **Award type:** 5
- **Project period:** 2019-08-15 → 2024-08-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976323

## Citation

> US National Institutes of Health, RePORTER application 9976323, Genetic regulation of antifungal drug resistance in Candida albicans (5F31DE028488-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9976323. Licensed CC0.

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