Candida albicans is the most prevalent human fungal pathogen accounting for nearly 20,000 deaths in the United States each year. C. albicans typically exists as a commensal of greater than 70% of individuals, and the majority of infections arise from the patients� own flora. Long thought to be asexual, a mating cycle in C. albicans was discovered just over a decade ago. Since then, many studies have looked at how the sexual cycle of C. albicans can play a role in commensalism and infection. In this work, I focus on two main components of the mating cycle. The first is the white-opaque phenotypic switch. This stochastic switch regulates both mating and pathogenesis of the organism, and has been shown to be strongly influenced by the environment, though no mechanism has been described. I show that a number of environmental stresses impact white-opaque switching via a common mechanism of affecting growth rate of the organism. Furthermore, I describe natural isolates that switch at different frequencies based on their growth rate. I discuss these findings in light of the recently described master regulator of white-opaque switching, Wor1. The second component of the mating cycle is that of pheromone signaling. I show that not all pheromone signaling is good, as prolonged exposure to pheromone can result in death in a subpopulation of cells. More interesting, however, is the discovery of same-sex mating in C. albicans. This process is shown to be driven by pheromone signaling, as strains that have augmented pheromone signaling are capable of mating without a traditional mating partner. Furthermore, I show that a diverse array of peptides that activate the canonical mating cascade can act to induce same-sex mating in C. albicans. These exciting discoveries are discussed in relation to how these new programs of mating have changed how we must look at the role of mating and interspecies interactions in eukaryotic pathogens.
Alby, Kevin A.,
"Mechanisms of pheromone signaling and same-sex mating in Candida albicans."
(2011).
Pathobiology Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.7301/Z0RV0KZ3
