Cell Wall Biogenesis in Candida albicans

白色念珠菌的细胞壁生物发生

基本信息

批准号：
8601170
负责人：
Stephen J. FREE
金额：
$ 7.82万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-01-01 至 2015-12-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The formation of the cell wall is a critical for the survival of Candida albicans and other fungal pathogens. Recent research advances in non-pathogenic fungi have demonstrated that a particular group of cross-linking enzymes can function to cross-link cell wall proteins into the cell wall. These cross-linking enzymes recognize oligosaccharides present on cell wall proteins and incorporate these oligosaccharides into the cell wall glucan/chitin matrix. The proteins are incorporated into the wall as part of this process The incorporation of cell wall proteins into the cell wall is a critical step in cell wall biogeness. The proposed pilot study will demonstrate that these cross-linking enzymes function in the cross-linking of cell wall proteins into the cell wall of C. albicans. The pilot study will also characterize the substrate specificity of the C. albicans cross-linking enzymes. Elements of the oligosaccharides present on the cell wall protein and elements of the glucan/chitin matrix must be recognized as substrates in order for the enzyme to cross-link the protein into the wall. The pilot study will help identify what specific characteristics of the oligosaccharides are important for the cross-linking reaction. The research will also determine what elements in the glucan/chitin matrix are used by the enzyme. An understanding of the cross-linking enzymes' substrate requirements will play a key role in the development of antifungal agents that act as inhibitors of these cross-linking enzymes. Relevance: Candida albicans is an important human pathogenic fungus. Invasive infections by C. albicans and other fungal pathogens are a major health concern for immunocompromised patients. Such infections are difficult to treat and have a high mortality rate. The proposed pilot study will examine whether a newly discovered group of enzymes that have been shown to function in the biogenesis of the fungal cell wall in non-pathogenic fungi, are critical for the growth and survival of C. albicans. A demonstration that these enzymes are needed for cell wall biosynthesis in C. albicans will highlight the possibility o targeting these enzymes for the development of an antifungal agent to treat invasive Candidiasis and other invasive fungal infections.

描述（由申请人提供）：细胞壁的形成对于白色念珠菌和其他真菌病原体的存活至关重要。非致病真菌的最新研究进展表明，一组特定的交联酶可以在细胞壁上交联细胞壁蛋白。这些交联酶识别存在于细胞壁蛋白上的寡糖，并将这些寡糖掺入细胞壁葡萄糖/几丁质基质中。作为此过程的一部分，将蛋白质掺入壁中，将细胞壁蛋白掺入细胞壁是细胞壁生物性的关键步骤。拟议的试点研究将证明这些交联酶在细胞壁蛋白的交联到白色念珠菌的细胞壁中的交联。试点研究还将表征白色念珠菌交联酶的底物特异性。存在于细胞壁蛋白上的寡糖的元素和葡萄糖/壳蛋白基质的元素必须被识别为底物，以使酶将蛋白质交联进入壁。试点研究将有助于确定寡糖的特定特征对于交联反应很重要。该研究还将确定酶使用葡萄糖/几丁质基质中的哪些元素。对交联酶的底物需求的理解将在抗真菌剂的发展中起关键作用，这些抗真菌剂充当这些交联酶的抑制剂。相关性：白色念珠菌是一种重要的人类致病真菌。白色念珠菌和其他真菌病原体的侵入性感染是免疫功能低下的患者的主要健康问题。这种感染很难治疗并且死亡率很高。拟议的试点研究将检查新发现的一组已显示在非致病真菌中真菌细胞壁的生物发生中起作用的酶是否对白色念珠菌的生长和存活至关重要。一个证明这些酶是白色念珠菌中细胞壁生物合成所需的，将强调靶向这些酶以开发抗真菌剂来治疗侵入性念珠菌病和其他侵入性真菌感染的可能性。