Assembly and Function of the Yeast Spore Wall

酵母孢子壁的组装和功能

• 批准号: 9768478
• 负责人: Aaron M Neiman
• 金额: $ 42.24万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-12 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9768478
• 关键词: Antifungal Agents; Appearance; Biochemistry; Biological Assay; Biological Models; Candida albicans; Cell Wall; Cell physiology; Cells; Chemical Structure; Chimera organism; Chitin Synthase; Chitosan; Complex; Cryptococcus neoformans; Cytology; Development; Drug Targeting; Encapsulated; Environment; Enzyme Inhibitor Drugs; Enzymes; Evolution; Genes; Genetic; Genetic Screening; Genome; Goals; Grant; HIV; Haploidy; Immunocompromised Host; In Vitro; Infection; Lipids; Mannans; Mass Spectrum Analysis; Mediating; Meiosis; Membrane; Molecular; Morphogenesis; Mycoses; Organelles; Pathway interactions; Patients; Pharmaceutical Preparations; Play; Polymers; Polysaccharides; Population; Public Health; Reaction; Regulation; Reproduction spores; Resistance; Role; Rupture; Saccharomyces cerevisiae; Saccharomycetales; Signal Transduction; Stress; Structure; Testing; Work; Yeast Model System; Yeasts; beta-Glucans; cancer therapy; dityrosine; drug development; drug resistant pathogen; effective therapy; enzyme activity; fungal genetics; fungus; gene function; glucan synthase; insight; metabolomics; novel; pathogenic fungus; polyphenol; resistant strain; side effect

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 β-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 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 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

7.项目总结/摘要 真菌感染是一个重要的公共卫生问题，也是治疗这些疾病的一个困难。 感染是少数可用的抗真菌药物。此外，现有的治疗方法既受到 严重的副作用和耐药菌株的频繁出现。细胞壁是一种重要的细胞器 真菌细胞。由于细胞壁对于生存力是必不可少的，因此抑制真菌细胞壁组装的药物是 潜在的抗真菌剂。事实上，目前的一种主要的抗真菌药物靶向β-葡聚糖合酶，这是一种关键的酶。 细胞壁合成酶。在芽殖酵母中，减数分裂产生的单倍体基因组被包裹起来 通过多层孢子壁，使孢子能够抵抗各种环境压力。内 孢子壁的各层由甘露聚糖和β-葡聚糖组成，类似于营养细胞壁。外 孢子壁的层由多糖壳聚糖、多酚二酪氨酸和第三， 被称为Chi的特征不佳的成分。这些孢子外壁成分在营养体中是不存在的 细胞壁，主要负责孢子的抗胁迫性。重要的是，尽管壳聚糖和 在芽殖酵母的营养细胞壁中不存在二酪氨酸，它们存在于致病性酵母的细胞壁中。 真菌芽殖酵母孢子壁为研究真菌壁提供了一个很好的模型系统 形态发生该基金的重点是了解保守酶的活性和调节 参与不同孢子壁成分的合成和组装，其长期目标是鉴定 抗真菌药物开发的新靶点