Assembly and Function of the Yeast Spore Wall

7. PROJECT SUMMARY/ABSTRACT Fungal infections are a significant public health problem because they can be lethal in immunocompromised individuals. A major difficulty in treating these infections is the small number of effective antifungal drugs. Existing treatments cause significant side effects and frequently result in the appearance of resistant strains. The cell wall is an essential organelle of a fungal cell and contains many fungal-specific components that are potential targets for anti-fungal drugs. For example, one major class of antifungal drugs targets a key enzyme in cell wall assembly. Therefore, understanding how the cell wall is constructed is essential for identifying new targets for antifungal drugs. In the budding yeast Saccharomyces cerevisiae, the haploid genomes produced by meiosis are encapsulated by a multi-layered spore wall, which allows spores to resist a variety of environmental stresses. The inner layers of the spore wall are composed of mannan and β- glucan, similar to the vegetative cell wall. The outer layers of the spore wall are comprised of the polysaccharide chitosan, the polyphenol dityrosine and triglycerides. These outer spore wall components are absent from vegetative cell walls and are primarily responsible for the stress resistance of spores. The combination of (1) chitosan, (2) a polyphenol, and (3) neutral lipids is a conserved structural module in fungal cell walls, including those of pathogenic fungi. The budding yeast spore wall therefore provides an excellent model system to study the construction and regulation of this structural module. This grant is focused on how a conserved set of lipid-droplet localized proteins regulates the assembly of this fungal cell wall structural module both in S. cerevisiae and the pathogen Candida dubliniensis.