A tractable nematode model for the emerging fungal pathogen, Candida auris

<p><em>Candida auris</em> is an emerging multidrug-resistant opportunistic fungal pathogen. It</p> <p>poses a significant threat to immunocompromised patients and those with prolonged stays in</p> <p>healthcare facilities. <em>C. auris</em> spreads rapidly in health care facilities through enhanced</p> <p>colonization of skin and abiotic surfaces. The genetic factors contributing to this ability and to</p> <p>the virulence, drug resistance, and stress-tolerant nature of <em>C. auris</em> are largely unknown.</p> <p>Current animal models of <em>C. auris</em> infections are not well standardized and report conflicting</p> <p>results. Additional animal models of virulence are needed, especially those amenable to high-</p> <p>throughput analysis. The nematode <em>Caenorhabditis elegans</em> has been validated as an effective</p> <p>tool for studying multiple fungal and bacterial pathogens. In this thesis, I describe a <em>C. elegans</em></p> <p>infection model in which <em>C. auris</em> is lethal to worms with kinetics similar to those observed for</p> <p><em>C. albicans</em>. However, <em>C. auris</em> does not form hyphae, indicating distinct virulence</p> <p>mechanisms. Furthermore, a mutant auxotrophic for adenosine (<em>ade2</em>Δ) is avirulent in this</p> <p>model, demonstrating that the nematode can discriminate between virulent and avirulent</p> <p>strains. The <em>C. elegans</em> model also recapitulates strain-to-strain variability in virulence</p> <p>observed in mouse models. In addition, I have adapted a live/dead staining methodology using</p> <p>SYTOX Orange to enable a high-throughput assay suitable for analyzing multiple strains or</p> <p>genetic mutants. Finally, I used this high-throughput assay to screen an insertion mutant library</p> <p>viifor avirulent mutants and identified several potential novel virulence factors. This model has</p> <p>significant advantages relative to other invertebrate virulence models for <em>C. auris</em> and is a</p> <p>beneficial complement to the more challenging and variable murine models.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2026

Authors dc:creator

• Martinez, Melissa
• <p>https://orcid.org/0000-0002-0359-7362</p>

Contributors dc:contributor

• Michael Lorenz, PhD
• Danielle Garsin, PhD
• Theresa M. Koehler, PhD

• Candida auris
• Candidozyma auris
• Caenorhabditis elegans
• Animal Model
• Animal Experimentation and Research
• Microbiology
• Pathogenic Microbiology

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1506

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-2563