REGULATION OF DIMORPHISM IN CANDIDA ALBICANS

白色念珠菌二态性的调控

• 批准号: 2900784
• 负责人: William A. Fonzi
• 金额: $ 24.22万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2900784
• 关键词: Candida albicans; acidity /alkalinity; biological polymorphism; cell wall; developmental genetics; enzyme activity; fluorescence microscopy; fungal genetics; gene deletion mutation; gene expression; genetic regulation; histogenesis; hydrolase; immunofluorescence technique; molecular cloning; mutant; nucleic acid sequence; polysaccharides; reporter genes; site directed mutagenesis; transferase

Candida albicans is the most often cited agent of opportunitistic fungal infections. The incidence of candidal infections have increased substantially over the past decade and concerns over this trend are heightened by the lack of efficacious treatments and high mortality rates. Despite a voluminous literature on C. Albicans, dealing largely with diagnostic techniques and research into its pathogenicity, much of its biology remains hidden. The mechanism(s) of pathogenesis continues to be a topic of conjecture and debate, however, the dimorphic ability of C. Albicans is regarded a significant contributing factor. The investigator previously identified several candidal genes differentially expressed in relation to the dimorphic response. One of these genes, PHR1, is transcriptionally regulated in responses to ambient pH, an environmental signal known to modulate the dimorphic transition of C. Albicans. A second pH-regulated gene, PHR2, encodes a structural and functional homolog of PHR1. Genetic studies have demonstrated that both are required for morphogenesis and virulence and probably encode an essential cell function. Preliminary studies suggest that these genes encode a glycosidase/glycosyl transferase activity that participates in cell wall assembly. While this function is not specific to hypase, the investigator has found a hyphal-specific gene that is dependent upon PHR1 expression. This indicates that the progression of morphogenesis is monitored by the cell and that for some hyphal-specific genes, expression is directly linked to morphogenesis. The investigator has proposed a series of biochemical and genetic experiments to further define the structure and function of the proteins encoded by PHR1 and PHR2 and to define the molecular mechanism(s) that integrate morphogenesis with hyphal-specific gene expression. This information will provide fundamental insights into the process of candidal morphogenesis and will contribute to the investigators long term objective of understanding the molecular basis of dimorphism and its role in pathogenesis.

白色念珠菌是最常被引用的机会性病原体。 真菌感染 念珠菌感染的发病率 在过去十年中， 由于缺乏有效的治疗方法， 和高死亡率。 尽管有大量关于C. Albicans，主要涉及诊断技术和研究 它的致病性，它的大部分生物学仍然是隐藏的。 的 发病机制仍然是一个主题， 猜想和争论，然而，C. Albicans被认为是一个重要的影响因素。 的 研究人员先前鉴定了几种念珠菌基因 差异表达与二型反应有关。 这些基因之一，PHR 1，是转录调控，在 对环境pH值的响应，已知的环境信号， 调节C.白人 第二 pH调节基因PHR 2编码一种结构和功能基因 PHR 1的同源物。 遗传学研究表明，两者都是 形态发生和毒力所需，可能编码一种 细胞的基本功能 初步研究表明， 基因编码糖苷酶/糖基转移酶活性， 参与细胞壁组装。 虽然该功能不是 研究人员发现了一种菌丝特异性 依赖于PHR 1表达的基因。 这表明 形态发生的进程由细胞监测， 对于一些菌丝特异性基因，表达是直接 与形态发生有关 研究人员提出了一系列 生物化学和遗传学实验，以进一步确定 PHR 1和PHR 2编码蛋白的结构和功能 并定义整合的分子机制 菌丝特异性基因表达的形态发生。 这 信息将提供对过程的基本见解 念珠菌形态发生，并将有助于 研究人员的长期目标是了解分子 二型性的基础及其在发病中的作用。