Assembly and Function of the Yeast Spore Wall

7.项目摘要/摘要 真菌感染是一个重大的公共卫生问题，因为它们在 免疫功能受损的个体。治疗这些感染的一个主要困难是有效的数量很少。 抗真菌药物。现有的治疗方法会引起显著的副作用，并经常导致出现 耐药菌株。细胞壁是真菌细胞的重要细胞器，含有许多真菌特有的细胞器。 可能成为抗真菌药物靶点的成分。例如，一大类抗真菌药物 靶向细胞壁组装中的一种关键酶。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。在萌芽酵母酿酒酵母中， 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 能抵抗各种环境压力。孢子壁内层由甘露聚糖和β组成。 葡聚糖，类似于营养细胞壁。孢子壁的外层由 壳聚糖多糖、多酚二氢赖氨酸和甘油三酯。这些外孢子壁成分是 不存在于营养细胞壁，主要负责孢子的抗逆性。这个 (1)壳聚糖、(2)多酚和(3)中性脂的组合是真菌中保守的结构模块 细胞壁，包括病原真菌的细胞壁。因此，萌芽酵母孢子壁提供了一种极好的 模型体系，研究该结构模块的构造和规范。这笔赠款的重点是如何 一组保守的脂滴定位蛋白调节这个真菌细胞壁结构模块的组装 在酿酒酵母和病原菌都柏林假丝酵母中都有。

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.