Description
- Abstract:
- Candidiasis is caused by fungi of the Candida genus and can range from mild to life-threatening systemic infections. In the United States, Candida bloodstream infections rank as the fourth most common cause of invasive bloodstream infections. Assessment of Candida virulence mechanisms could advance current understanding of Candida infections and improve diagnosis and treatment. CHROMagar medium has been used for the quick assessment of Candida species due to colonies forming species-specific colors. Candida albicans usually exhibit a standard white color, but previous studies from our lab showed that C. albicans variants can alter the color on CHROMagar, resulting in differences within a single Candida species. It had been further demonstrated that C. albicans white-opaque cell states, or C. albicans mutants such as those lacking EFG1 were distinguishable on CHROMagar. Understanding the mechanisms underlying such color variations could broaden the potential applications of CHROMagar medium and further enable the assessment of different C. albicans cell states. In this thesis, the genetic mechanisms behind colony color variation on CHROMagar was investigated by analysis of a collection of clinical C. albicans isolates. Whole-genome-sequencing revealed that a number of clinical isolates could adopt a purple colony color and that a number of these had gained an extra copy of chromosome R. Color change was also observed in euploid strains with two strains associated with homozygous EFG1 mutations resulting in a distinct phenotypic state. Crispr-Cas9 editing was employed to delete the left or right arm of the one copy of chromosome R (chrR) in strains trisomic for this chromosome. We further narrowed down the region on chrR associated with the color change on CHROMagar, specifically a region composed of 279 genes on the left arm of chR. In line with previous studies, we observed that chromosome R trisomy led to increased triazole resistance, and identified a region on chromosome R associated with this resistance. Together, these results demonstrate that changes to chromosome R copy number regulate C. albicans CHROMagar color variation and fluconazole resistance in multiple clinical isolates. These findings provide insights into C. albicans aneuploidy, phenotypic plasticity, and antifungal drug susceptibility.
- Notes:
- Thesis (Sc. M.)--Brown University, 2025
Citation
Yin, dannie,
"Aneuploidy of Chromosome R Regulates Candida albicans Colony Color Variations on CHROMagar Media"
(2025).
Biotechnology, Biology and Medicine Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:99yb6au5/
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Biology and Medicine Theses and Dissertations
Theses and Dissertations for the Biology and Medicine department....