Fungal infections are caused by a variety of fungi, and with a variety of clinical manifestations. Antifungal treatments are limited due to host toxicity and fungi gaining resistance. By utilizing the model organism Saccharomyces cerevisiae, we hope to elucidate the molecular mechanisms of fungal pathogenesis that we can then validate in the human pathogen Candida albicans, as well as explore options for novel therapies. Small molecule signaling is a method by which single-cell organisms can communicate with one another, enabling them to coordinate gene expression. This is a useful tool because it allows microbes to turn on phenotypes that are only valuable when done in large numbers, such as bioluminescence, or virulence traits. We have previously shown that the yeast Saccharomyces cerevisiae synthesizes the secondary metabolite indole-3-acetic acid (IAA) from tryptophan. IAA is secreted into the environment, where it acts as a signal. At low concentrations, the IAA signals yeast to induce virulence traits, while at high concentrations, it is lethal. The purpose of this thesis was to investigate the molecular mechanism of IAA (plant hormone auxin) regulation in fungi, specifically, Saccharomyces cerevisiae and the human pathogen Candida albicans. Towards this end, I first focused my efforts on evaluating the role of S. cerevisiae Grr1, as a putative IAA receptor. By evaluating the IAA response of several Grr1 mutants, I was able to show that the leucine-rich repeat region, while not required for function, likely plays a significant role in maintaining the structural integrity of the protein. Next, I evaluated IAA associated phenotypes, such as filamentation, surface adhesion and IAA uptake of the grr1 null mutant in the human pathogen Candida albicans. Together, these data support the hypothesis that GRR1 regulates IAA response, probably by regulating the IAA uptake carriers.
| Identifer | oai:union.ndltd.org:wpi.edu/oai:digitalcommons.wpi.edu:etd-theses-1687 |
| Date | 03 May 2012 |
| Creators | Perelta, Alisha Nicole |
| Contributors | Elizabeth F. Ryder, Committee Member, Reeta Prusty Rao, Advisor, Tanja Dominko, Committee Member |
| Publisher | Digital WPI |
| Source Sets | Worcester Polytechnic Institute |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Masters Theses (All Theses, All Years) |
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