# Mechanisms of Candida auris skin colonization

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $242,250

## Abstract

ABSTRACT
C. auris is a relatively new opportunistic fungal pathogen that is spreading worldwide with high rates of intrinsic
resistance to antifungal antibiotics and a strong affinity for human skin. It is now ranked by the CDC as the top
drug-resistant fungal threat. Epidemiological analysis suggests that pathogen transmission occurs efficiently in
shared housing environments such as hospitals or nursing homes. Importantly, person-to-person transmission
of skin-associated yeasts appears to be a primary mode of spread. Although C. auris skin colonization is
asymptomatic, life-threatening disease can arise in patients with additional risk factors, such as
immunosuppression, intravenous catheter placement, surgery, and antibiotics. Understanding of the molecular
mechanisms by which C. auris tenaciously colonizes the skin might offer potential opportunities to interrupt the
infection cycle. Unfortunately, no molecules been identified that are important for host skin colonization. To begin
to address this problem, we have established three mouse models of skin colonization and epicutaneous
infection with Candida albicans that are suitable for investigations of C. auris. Using these models, we observe
significantly higher titers of C. auris than C. albicans. Unlike C. albicans, C. auris fails to induce skin damage or
to induce expression of the key antifungal pro-inflammatory cytokine, IL-17. Notably, C. auris displays clusters
of yeast in the epidermis as well as invasion of the hair follicles, neither of which are seen with C. albicans. In a
forward genetic screen of ~700 C. albicans null mutants, we identified four genes required for epicutaneous
infection of skin. We disrupted the C. auris orthologs using a CRISPR/Cas9-based protocol. We found that all
four mutant displayed defects in skin colonization in C. auris. Notably, two of the four genes encode C. auris
orthologs of components of the HOG MAP kinase signaling pathway and are required for effective skin
colonization in all three models. These data lead us to hypothesize that the HOG MAPK signaling pathway
controls skin colonization in C. auris by controlling the expression of downstream target genes. We hypothesize
that one or more of these target genes will be involved in promoting the ability of C. auris to effectively colonize
the skin. We will test this high-risk/high-payoff hypothesis by 1) Investigating the role of the C. auris Hog1
pathway in skin colonization and establishing its role in gene regulation and 2) Identifying effectors of C. auris
skin colonization. These studies have the potential to identify molecules and mechanisms required for C. auris
to colonize the skin, a central aspect of the infection cycle of this important emerging drug-resistant pathogen.
Having laid the groundwork, we are in a strong position to accomplish these goals, which we anticipate will
provide a foundation to begin to obtain molecular insights into the unique biology of C. auris.

## Key facts

- **NIH application ID:** 10509882
- **Project number:** 1R21AI171789-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** SUZANNE M NOBLE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $242,250
- **Award type:** 1
- **Project period:** 2022-05-20 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10509882

## Citation

> US National Institutes of Health, RePORTER application 10509882, Mechanisms of Candida auris skin colonization (1R21AI171789-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10509882. Licensed CC0.

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