Author ORCID Identifier

https://orcid.org/0000-0002-0359-7362

Date of Graduation

5-2026

Document Type

Dissertation (PhD)

Program Affiliation

Microbiology and Infectious Diseases

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Michael Lorenz, PhD

Committee Member

Danielle Garsin, PhD

Committee Member

Theresa M. Koehler, PhD

Committee Member

Ambro van Hoof, PhD

Committee Member

Christian Perez, PhD

Committee Member

Catherine Denicourt, PhD

Abstract

Candida auris is an emerging multidrug-resistant opportunistic fungal pathogen. It

poses a significant threat to immunocompromised patients and those with prolonged stays in

healthcare facilities. C. auris spreads rapidly in health care facilities through enhanced

colonization of skin and abiotic surfaces. The genetic factors contributing to this ability and to

the virulence, drug resistance, and stress-tolerant nature of C. auris are largely unknown.

Current animal models of C. auris infections are not well standardized and report conflicting

results. Additional animal models of virulence are needed, especially those amenable to high-

throughput analysis. The nematode Caenorhabditis elegans has been validated as an effective

tool for studying multiple fungal and bacterial pathogens. In this thesis, I describe a C. elegans

infection model in which C. auris is lethal to worms with kinetics similar to those observed for

C. albicans. However, C. auris does not form hyphae, indicating distinct virulence

mechanisms. Furthermore, a mutant auxotrophic for adenosine (ade2Δ) is avirulent in this

model, demonstrating that the nematode can discriminate between virulent and avirulent

strains. The C. elegans model also recapitulates strain-to-strain variability in virulence

observed in mouse models. In addition, I have adapted a live/dead staining methodology using

SYTOX Orange to enable a high-throughput assay suitable for analyzing multiple strains or

genetic mutants. Finally, I used this high-throughput assay to screen an insertion mutant library

viifor avirulent mutants and identified several potential novel virulence factors. This model has

significant advantages relative to other invertebrate virulence models for C. auris and is a

beneficial complement to the more challenging and variable murine models.

Keywords

Candida auris, Candidozyma auris, Caenorhabditis elegans, Animal Model

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