Assembly and Function of the Yeast Spore Wall

7.项目总结/摘要 真菌感染是一个重大的公共卫生问题，因为它们在人类中可能是致命的。 免疫力低下的人。治疗这些感染的一个主要困难是有效药物的数量很少。 抗真菌药物现有的治疗方法会引起严重的副作用，并经常导致出现 耐药菌株细胞壁是真菌细胞的基本细胞器，含有许多真菌特异性的 这些成分是抗真菌药物的潜在靶点。例如，一种主要的抗真菌药物 靶向细胞壁组装中的关键酶。因此，了解细胞壁是如何构建的， 对于确定抗真菌药物的新靶点至关重要。在芽殖酵母酿酒酵母中， 由减数分裂产生的单倍体基因组被多层孢子壁包裹，这使得孢子能够 抵抗各种环境压力。孢子壁的内层由甘露聚糖和β-甘露聚糖组成， 葡聚糖，类似于营养细胞壁。孢子壁的外层由 多糖壳聚糖、多酚二酪氨酸和甘油三酯。这些外部孢子壁成分是 在营养细胞壁中不存在，并且主要负责孢子的抗逆性。的 （1）壳聚糖、（2）多酚和（3）中性脂质的组合是真菌中保守的结构模块 细胞壁，包括致病真菌的细胞壁。因此，芽殖酵母孢子壁提供了极好的 模型系统，研究该结构模块的构建与调控。该基金的重点是如何 一组保守的脂滴定位蛋白质调节这种真菌细胞壁结构模块的组装 在S.酿酒酵母和病原体都柏林假丝酵母。

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.