Farnesol Signaling in Candida albicans

Candida albicans is a polymorphic fungus that causes a range of disease in humans, from mucosal infections to systemic disease. Its ability to cause disease is linked to conversion between yeast and filamentous forms of growth, and the first quorum-sensing molecule discovered in an eukaryote, farnesol, blocks this transition. In C. albicans, farnesol also kills mating-competent opaque cells, inhibits biofilm formation, protects the cells from oxidative stress, and can be a virulence factor or protective agent in disseminated and mucosal mouse models of infection, respectively. While much emphasis has been placed on determining its effect on C. albicans morphology, the molecular response to farnesol is not completely understood. The overall theme for this dissertation was to better understand the C. albicans molecular response to farnesol under quorum sensing conditions. Due to the duplicitous nature of the farnesol response in C. albicans, i.e., its ability to kill cells or simply alter morphology, we clearly defined the environmental conditions in which farnesol acts as a quorum sensing molecule or as a toxic agent towards C. albicans. This clarification enabled a subsequent two-pronged approach to study the molecular response to farnesol during morphological regulation. A direct approach was used to investigate the role of a likely candidate, Tup1, a negative regulator of hyphal development, in farnesol signaling. Secondly, a screening approach was utilized to identify new farnesol resistant mutants that may participate in the farnesol response. From the mutants identified, Czf1 (C. albicans zinc finger) was selected for further characterization and was shown to play a vital role in the morphological response to farnesol as well as farnesol tolerance. Overall, this study identified two new factors involved in farnesol signaling, and highlights the power of farnesol as a tool with which to unravel the complex signaling networks present in C. albicans. Advisor: Audrey L. Atki