Assembly and Function of the Yeast Spore Wall

酵母孢子壁的组装和功能

• 批准号: 10000768
• 负责人: Aaron M Neiman
• 金额: $ 40.54万
• 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/10000768
• 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。项目摘要/摘要 真菌感染是一个重大的公共卫生问题，而在治疗这些方面很难 感染是少量可用的抗真菌药物。此外，现有治疗既遭受 明显的副作用和抗性菌株的经常出现。细胞壁是必不可少的细胞器 真菌细胞。因为细胞壁对于生存能力至关重要，所以抑制真菌细胞壁组件的药物是 潜在的抗真菌剂。实际上，一类主要的当前抗真菌剂靶向β-葡聚糖合酶，这是一个键 细胞壁合成中的酶。在萌芽的酵母中，减数分裂产生的单倍体基因组被封装 通过多层扰流板壁，孢子可以抵抗各种环境应力。内心 锅炉层的层由曼南和β-葡聚糖组成，类似于蔬菜细胞壁。外部 盘壁的层累积了多糖壳聚糖，多酚二易酮和第三个 表征不佳的成分称为CHI。这些外部变质壁组件不存在于蔬菜中 细胞壁和原发性负责孢子的应力抗性。重要的是，尽管壳聚糖和 在发芽酵母中的营养细胞壁上不存在丁香氨酸，它们存在于致病性的壁中 真菌。因此，发芽的酵母孢子墙为研究真菌墙提供了出色的模型系统 形态发生。该赠款的重点是理解组成酶的活动和调节 参与了不同的破坏墙组件的合成和组装，其长期目标是识别 抗真菌药物开发的新目标