# Quantitative genetic approaches to Candida albicans pathogenesis

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2020 · $421,704

## Abstract

ABSTRACT
 Candida albicans is a common fungal commensal and opportunistic pathogen occupying the skin, oral
cavity, gastrointestinal tract, and genitourinary tract of its human host. Overgrowth of C. albicans within these
host niches can lead to mucosal and systemic disease and typically relies on pathogenic processes such as
the yeast-hyphal transition. Hyphae are capable of breaching host mucosal barriers through active penetration
and endocytic uptake that both lead to host cell destruction and transmigration of C. albicans to deeper tissues.
Thus, host epithelial cells serve a vital role in detecting C. albicans overgrowth and signaling to professional
phagocytes to remove invasive fungal cells. Interestingly, natural C. albicans isolates obtained from clinical
setting display a range of filamentation phenotypes, including strains unable to produce hyphae. Here, we will
investigate the genetic determinants underlying natural occurring phenotypic variation in C. albicans that
regulates the ability to filament and/or colonize the oral cavity through the first use of quantitative genetic
approaches in C. albicans. A genetically diverse set of sequenced clinical C. albicans isolates forms the basis
of this study as they display significant variation in filamentation processes in vitro and the ability to cause
disease in vivo. First, gene expression across the sequenced isolates will facilitate construction of co-
expression network modules that associate with in vitro filamentation phenotypes. Expression of key
transcriptional regulators within each predicted module will be tested in multiple strain backgrounds for altered
in vitro filamentation across a variety of solid and liquid substrates. Automated phenotyping of filamentation,
adhesion, and invasion of agar substrates will be built to facilitate scoring mutant phenotypes (Aim 1). In Aim 2,
quantitative trait loci (QTL) mapping will be developed utilizing the parasexual program, an alternative mating
and ploidy reduction system in C. albicans, to identify the genes responsible for differences in filamentation
and epithelial damage between C. albicans strains incubated with OKF6/TERT-2 oral epithelial cells. Identified
genes that modulate filamentation and epithelial damage in tissue culture systems will be subsequently tested
for in vivo colonization and filamentation phenotypes of a murine model of oropharyngeal candidiasis.
Preliminary experiments suggest that filamentation and damage of oral epithelial cells are separable
phenotype, which will be explored further through dual-species RNA sequencing of strains separated by
filamentation (+/-) and cell damage (+/-) phenotypes incubated with OKF6/TERT-2 cells (Aim 3). This Aim will
also determine the role of recently identified host genes with differential expression between damaging and
colonizing strains in host cell signaling and transcriptional responses that lead to either filamentation or host
cell damage during interaction with oral e...

## Key facts

- **NIH application ID:** 10052193
- **Project number:** 1R01AI148788-01A1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Matthew Z Anderson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $421,704
- **Award type:** 1
- **Project period:** 2020-05-12 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10052193

## Citation

> US National Institutes of Health, RePORTER application 10052193, Quantitative genetic approaches to Candida albicans pathogenesis (1R01AI148788-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10052193. Licensed CC0.

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