Regulation of Morphogenesis in C. albicans

白色念珠菌形态发生的调控

• 批准号: 6330928
• 负责人: James B Konopka
• 金额: $ 22.25万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6330928
• 关键词: Candida albicans; binding proteins; cell cycle; cell cycle proteins; fungal genetics; fungal proteins; green fluorescent proteins; microorganism culture; mutant; posttranslational modifications; protein structure function; site directed mutagenesis; virulence

The goal of this proposal is to determine the molecular mechanisms of morphogenesis for Candida albicans. C. albicans is the most common fungal pathogen in humans and causes particularly severe life-threatening infections in immunocompromised individuals. The significance of C. albicans as a health risk is increasing as better medical techniques make long-term care of organ transplant, cancer, and HIV patients more common. A better understanding of the mechanisms of pathogenesis is needed to formulate new therapeutic strategies to combat Candidiasis because the drugs currently used against C. albicans are not very effective, especially after it has invaded into tissues. One virulence factor that has been strongly implicated in the pathogenesis of C. albicans is the ability of this yeast to undergo morphological transitions between round budding cells and filamentous hyphae. Therefore, the specific aims of this grant are designed to identify the proteins that regulate morphogenesis of C. albicans. In particular, the septin family of cytoskeletal proteins will be examined because the septins play important roles in morphological transitions in the yeast S. cerevisiae and other organisms. Genetic strategies will be used to determine which members of the septin family function in hyphal morphogenesis. Biochemical approaches will then be used to study the mechanisms that regulate C. albicans septin proteins, and targeted mutagenesis will be used to determine their role in controlling hyphal morphogenesis. Septins act by recruiting key regulatory proteins. Therefore, Septin function in C. albicans will be defined further by identifying septin-binding proteins and analyzing their function. The experimental procedures are designed to take full advantage of recently improved strategies for the genetic analysis of C. albicans and the data being made available from the C. albicans genome sequencing project. Altogether, these studies are expected to identify key regulators of morphological transitions that promote the pathogenesis of C. albicans.

本研究的目的是确定白色念珠菌形态发生的分子机制。 C.白色念珠菌是人类中最常见的真菌病原体，并且在免疫功能低下的个体中引起特别严重的危及生命的感染。 C.随着更好的医疗技术使器官移植、癌症和艾滋病患者的长期护理更加普遍，白色念珠菌作为一种健康风险正在增加。 由于目前抗念珠菌病的药物还不多，因此需要更好地了解其发病机制，以制定新的治疗策略。白色念珠菌不是很有效，特别是在它侵入组织后。一种与C.白色念珠菌是这种酵母经历圆形出芽细胞和丝状菌丝之间的形态转变的能力。 因此，该基金的具体目标是鉴定调节C.白色念珠菌 特别地，将检查细胞骨架蛋白的septin家族，因为septins在酵母S中的形态转变中起重要作用。酿酒酵母和其他生物。 遗传策略将被用来确定哪些成员的隔蛋白家族功能的菌丝形态发生。 生物化学方法将被用来研究调节C。白念珠菌septin蛋白，和定向诱变将用于确定它们在控制菌丝形态发生中的作用。 Septins通过募集关键的调节蛋白发挥作用。 因此，Septin在C.将通过鉴定septin结合蛋白并分析其功能来进一步确定白色念珠菌。 实验程序的设计，以充分利用最近改进的策略，遗传分析的C。白色念珠菌和数据可从C.白念珠菌基因组测序计划。 总之，这些研究有望确定促进C.白色念珠菌。