Global Distribution, Epidemiology and Genetics of Infectious Yeast Cryptococcus deneoformans and Other Soil Yeasts

Abstract

Yeasts, broadly defined as unicellular fungi, have a disproportionate impact on human health and economy despite comprising less than 1% of the fungal kingdom. Soil is a primary yeast habitat where they play essential roles in decomposition, nutrient cycling and as food sources for other soil dwellers. Cryptococcus deneoformans is a basidiomycetous yeast commonly found in soil in association with pigeon droppings. As an opportunistic pathogen of humans, it contributes to 181,000 deaths caused by cryptococcosis and fungal meningitis worldwide every year. Significant intraspecific variation in melanin synthesis, an essential virulence factor of C. deneoformans, is observed in natural populations, with its genetic basis remaining largely unknown. My thesis investigated global patterns in soil yeast diversity where we identified mean annual precipitation and international human travel as two, strong predictors of soil yeast diversity worldwide. We discovered a novel C. deneoformans population in Saudi Arabian desert soils, likely a recent introduction to the region facilitated by anthropogenic activities. Using bulk segregant analysis and gene expression assays, we identified six, novel candidate genes that potentially contribute to intraspecific melanin variance in C. deneoformans. Finally, we investigated genome-wide allele distribution patterns in hybrid strains derived from mating between C. deneoformans and its sister species, C. neoformans. Significantly skewed allele distributions we detected in hybrid genomes highlight the genomic incompatibilities between the two species and support their classification into two, distinct species which has been a topic of much debate. Overall, my PhD thesis makes several contributions to our understanding of soil yeast communities, genetics of virulence factors in C. deneoformans, and outcomes of hybridization between fungal lineages.