REGULATION OF DIMORPHISM IN CANDIDA ALBICANS

白色念珠菌是最常被引用的机会主义病原体 真菌感染。念珠菌感染的发生率有 在过去十年中大幅增加，人们对 缺乏有效的治疗方法加剧了这一趋势 和高死亡率。尽管有大量关于C. 白念珠菌，主要涉及诊断技术和研究 由于它的致病性，它的大部分生物学特性仍然隐藏着。这个 发病机制(S)继续是一个话题 然而，猜想和争论表明，C. 白念珠菌被认为是一个重要的致病因素。这个 研究人员此前发现了几种念珠菌基因 与二态反应相关的差异表达。 其中一个基因Phr1在转录水平上受 对环境pH的反应，这是一种已知的环境信号 调节白色念珠菌的二态转变。一秒钟 PH调节基因PHR2编码一种结构和功能 Phr1的同源基因。遗传学研究表明，这两种基因都是 是形态发生和致病性所必需的，可能编码一种 基本的细胞功能。初步研究表明，这些 编码糖苷酶/糖基转移酶活性的基因 参与细胞壁组装。而此函数不是 针对发酵酶，调查人员发现了一种特定于菌丝的 依赖于Phr1表达的基因。这表明， 形态发生的进展由细胞和 对于一些菌丝特异的基因，表达是直接的 与形态发生有关。调查员提出了一系列 生化和基因实验，以进一步定义 Phr1和PHR2编码蛋白的结构和功能 并对整合的分子机制进行了界定(S 菌丝特异性基因表达的形态发生。这 信息将提供对这一过程的基本见解 念珠菌的形态发生，并将有助于 研究人员了解分子的长期目标 二型性的基础及其在发病机制中的作用。

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.