# Complex haploinsufficiency based genetic analysis of C. albicans pathogenesis

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2020 · $540,362

## Abstract

PROJECT SUMMARY
Candida albicans is an important opportunistic pathogen for people living with HIV/AIDS and primarily causes
mucosal diseases such as oropharyngeal candidiasis (OPC) and esophageal candidiasis (EC). In the era of
antiretroviral therapy (ART), C. albicans remains the most common fungal pathogen affecting those with
HIV/AIDS and OPC is one of the most common infections in HIV patients with mild-to-moderate
immunosuppression (CD4 counts 200-500). The pathogenesis of OPC can be separated into two stages: 1)
C. albicans adhesion/biofilm formation on the mucosal surface and 2) hyphae-mediated invasion of the
epithelium and submucosal stroma with concomitant inflammation and tissue damage. Thus, OPC
pathogenesis is dependent on three of the most important mediators of C. albicans virulence: adhesion, biofilm
formation, and filamentation. Although each of these factors has been studied using specific C. albicans
mutants, no systematic large-scale genetic analysis of OPC pathogenesis has been undertaken. The goal of
this application is to define and characterize the transcriptional networks that underlay the ability of C. albicans
to cause oral disease. Recently, we have pioneered the use of complex haploinsufficiency (CHI)-based genetic
interaction analysis to understand the function of complex genetic networks. Here, we propose to use CHI
analysis to test the hypothesis that Cbk1 represents a master regulator of transcriptional processes critical for
OPC pathogenesis (Aim 1). In addition to this intra-pathway analysis, we will perform the first large-scale
genetic screens for, and CHI analyses of, TF networks required for murine oral candidiasis (Aim 2) and in vivo
filamentation (Aim 3). The screen in Aim 3 will utilize our novel intra-vital imaging assay to quantitatively
differentiate between yeast and filamentous cells in the sub-epithelial stroma of mice. This screen will not only
be the first in vivo C. albicans filamentation screen but also will allow us to distinguish TFs required for the
invasion stage of OPC from TFs required for the adhesion/biofilm formation stage.

## Key facts

- **NIH application ID:** 9830009
- **Project number:** 5R01AI133409-03
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Damian J Krysan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $540,362
- **Award type:** 5
- **Project period:** 2017-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830009

## Citation

> US National Institutes of Health, RePORTER application 9830009, Complex haploinsufficiency based genetic analysis of C. albicans pathogenesis (5R01AI133409-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9830009. Licensed CC0.

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