# Genetic circuitry governing skin colonization of Candida auris

> **NIH NIH F32** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $79,806

## Abstract

Abstract
 Candida auris is an emerging fungal pathogen causing invasive infections worldwide with a high mortality
rate. Unlike other fungal pathogens, it is frequently hospital-acquired and easily transmit within healthcare
facilities, making it a critical and urgent public health concern. A unique virulence trait of C. auris is its ability to
achieve extremely high levels of skin colonization, which not only serves as a source for nosocomial transmission
but also as a risk factor for the development of subsequent life-threatening bloodstream infections.
 In the model fungal pathogen Candida albicans, tissue adhesion and invasion are mediated by cell surface-
exposed proteins known as adhesins, which include the agglutinin-like sequence (ALS) protein family and
hyphal-regulated cell wall (Hyr/Iff) protein family. C. auris encodes genes homologous to characterized C.
albicans ALS and Hyr/Iff adhesin families. While the function and regulation of adhesins in tissue adhesion and
invasion have been explored to a limited extent in C. albicans, no mechanistic studies have investigated the
molecular machinery governing skin colonization in C. auris. C. auris clinical isolates identified so far are divided
into five independent clades, with Clades I, III, and IV being pathogenic and associated with outbreaks of invasive
infections. I, and others, have identified clade-specific abilities in colonizing skin by C. auris: Clade IV shows
higher skin colonization compared to Clade I even though they encode the same set of adhesin genes. Therefore,
I hypothesize that there is clade-specific genetic circuitry governing skin colonization in C. auris.
 To address this hypothesis, I will leverage the molecular genetic tools developed by our lab and my
established in vitro keratinocyte and in vivo animal models to determine the genetic mechanisms underlying skin
colonization in both Clade I and Clade IV. My preliminary data suggest that Clade I relies on specific adhesin
genes to adhere to keratinocytes. I will examine their roles in skin colonization using the in vivo murine model. I
also identified that Swi1, a component of the SWI/SNF chromatin remodeling complex, positively regulates the
transcription of adhesin genes in Clade I. I will characterize this transcriptional regulation by comparing
nucleosome occupancy at promoters of critical adhesin genes in both wild-type and SWI/SNF-deficient mutants,
along with assessing SWI/SNF enrichment. To investigate mechanisms contributing to the increased skin
colonization in Clade IV, I will first define the function of individual adhesins in keratinocyte adherence and in
vivo skin colonization by generating targeted mutations of adhesins in this clade. I will then employ an unbiased
forward genetics screen using high-throughput imaging-based analysis to identify additional genes required for
skin colonization in Clade IV. This approach has led to the discovery of two factors that substantially contribute
to keratinocyt...

## Key facts

- **NIH application ID:** 10820625
- **Project number:** 1F32AI181164-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Guolei Zhao
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $79,806
- **Award type:** 1
- **Project period:** 2024-08-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10820625

## Citation

> US National Institutes of Health, RePORTER application 10820625, Genetic circuitry governing skin colonization of Candida auris (1F32AI181164-01). Retrieved via AI Analytics 2026-06-13 from https://api.ai-analytics.org/grant/nih/10820625. Licensed CC0.

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