Research Project
10261376
7. PROJECT SUMMARY/ABSTRACT Fungal infections are a significant public health problem and one difficulty in treatment of these infections is the small number of available antifungal drugs. Moreover, existing treatments suffer both from significant side effects and the frequent appearance of resistant strains. The cell wall is an essential organelle of the fungal cell. Because the cell wall is essential for viability, drugs that inhibit fungal cell wall assembly are potential antifungal agents. Indeed, one major class of current antifungals targets ?-glucan synthase, a key enzyme in cell wall synthesis. In budding yeast, 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 ?-glucan, similar to the vegetative cell wall. The outer layers of the spore wall are comprised of the polysaccharide chitosan, the polyphenol dityrosine and a third, poorly characterized component termed Chi. These outer spore wall components are absent from vegetative cell walls and primarily responsible for the stress resistance of spores. Importantly, although chitosan and dityrosine are absent from vegetative cell walls in budding yeast, they are present in the walls of pathogenic fungi. The budding yeast spore wall therefore provides an excellent model system to study fungal wall morphogenesis. This grant is focused on understanding the activity and regulation of conserved enzymes involved in synthesis and assembly of different spore wall components with the long-term goal of identifying new targets for antifungal drug development
