Emma Bragdon

Document Type

Honors Thesis

Major

Biochemistry

Advisor(s)

Robert Wheeler

Committee Members

Edward Bernard, Joshua Kelley, Margaret Killinger, Melody Neely

Graduation Year

2021

Publication Date

2025

Abstract

Candida albicans (C. albicans) is a commensal yet opportunistic pathogen. It is typically found in the oropharyngeal, gastrointestinal, and reproductive tract of humans. While healthy adults are not infected by the pathogen besides the common vaginal yeast infection, immune-compromised individuals such as those going through chemotherapy and bone marrow transplants are susceptible to life-threatening infection with mortality rates reaching up to 40%. Understanding the mechanisms as to how this pathogen causes disease may help us develop new strategies to prevent and treat these lethal infections. We sought to identify new virulence genes in C. albicans that regulate the innate immune response. Since hyphal growth is tightly linked to virulence for C. albicans, we reasoned that novel immune evasion genes might be identified as mutations that affect hyphal growth or virulence, but not both. Previous work in the Wheeler Lab identified 133 mutants in the Noble mutant library collection which had previously been characterized to encode known secreted factors, or be required for hyphal growth or virulence, but not both. Using a zebrafish hindbrain infection model, where it is known that survival is closely linked to rapid immune responses, mutant C. albicans strains lacking single genes were injected into the hindbrain of the zebrafish, and infection was observed and analyzed to draw conclusions on virulence factors that are most important in C. albicans infection. This method identified two genes, CHT2 and ORF19.5547, that appear to be important in virulence. Further directions include determining the mechanisms by which these genes enhance virulence.

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