UC Merced

Fungal pathogens are responsible for millions of infections worldwide every year. These infections are caused by several fungal species, yet the Candida species of fungal pathogens are the most frequently isolated from humans. They cause superficial to life-threatening disseminated infections, where individuals with compromised immune systems, individuals with changes in their resident microbiota, and those undergoing antibiotic treatments are at highest risk for developing severe Candida infections. A longstanding limitation in the field is the ability to make precise genome edits in the Candida species to identify genes and pathways involved in virulence and antifungal resistance. Chapter 1 of this dissertation describes the identification of Candida albicans transcriptional regulators controlling cell aggregation in response to the antifungal drug caspofungin. This led to the identification of a novel adhesin mediating aggregation and a cell wall protein critical for the caspofungin response. Chapter 2 describes the development and optimization of the first markerless CRISPR/Cas9 system for genome editing in the emerging fungal pathogen Candida auris. I show the versatility of this tool to perform genome edits in clinical isolates and identify a conserved role for a transcription factor involved in the caspofungin response. Chapter 3 describes my work on the efficacy of a novel oxidizing disinfectant agent capable of disrupting biofilms, surface attached microbial communities, of pathogenic fungal and bacterial species. Finally, Chapter 4 summarizes my conclusions from the first three chapters and discusses future directions for the work. Overall, this body of work provides new tools for the genetic manipulation of an emerging fungal pathogen and expands our understanding of how Candida species respond to antifungal drug treatment.