Cell Wall Biogenesis in Candida albicans

白色念珠菌的细胞壁生物发生

• 批准号: 8429703
• 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
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8429703
• 关键词: Adhesions; Affect; Anabolism; Antifungal Agents; Aspergillus; Aspergillus fumigatus; Biogenesis; Candida; Candida albicans; Candidiasis; Cell Wall; Characteristics; Chitin; Cleaved cell; Development; Elements; Enzymes; Fostering; Fungi Model; Genes; Glucans; Glycoproteins; Growth; Health; Healthcare; Homologous Gene; Human; Immune system; Immunocompromised Host; Incidence; Indium; Infection; Link; Mannans; Microbial Biofilms; Mycoses; Neurospora crassa; Oligosaccharides; Pathogenesis; Patients; Pilot Projects; Play; Polymers; Polysaccharides; Process; Proteins; Reaction; Research; Research Project Grants; Resistance; Role; Series; Structure; Substrate Specificity; crosslink; environmental change; enzyme substrate; fungus; inhibitor/antagonist; link protein; mortality; mutant; novel; pathogen; public health relevance; receptor; research study; sensor

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生存至关重要。非病原真菌的最新研究进展表明，一组特定的交联酶可以发挥将细胞壁蛋白交联到细胞壁中的作用。这些交联酶识别 寡糖存在于细胞壁蛋白质上并将这些寡糖掺入细胞壁葡聚糖/几丁质基质中。作为该过程的一部分，蛋白质被掺入细胞壁中。细胞壁蛋白掺入细胞壁是细胞壁生物发生的关键步骤。 拟议的试点研究将证明这些交联酶在细胞壁蛋白交联到白色念珠菌细胞壁中发挥作用。该试点研究还将表征白色念珠菌交联酶的底物特异性。细胞壁蛋白质上存在的寡糖元素和葡聚糖/几丁质基质的元素必须被识别为底物，以便酶将蛋白质交联到细胞壁中。该初步研究将有助于确定寡糖的哪些具体特征对于交联反应很重要。该研究还将确定酶使用葡聚糖/甲壳质基质中的哪些元素。了解交联酶的底物要求将在开发作为这些交联酶抑制剂的抗真菌剂中发挥关键作用。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袭性感染是免疫功能低下患者的主要健康问题。此类感染难以治疗且死亡率很高。拟议的试点研究将检查一组新发现的酶是否对白色念珠菌的生长和生存至关重要，这些酶已被证明在非病原真菌的真菌细胞壁的生物发生中发挥作用。白色念珠菌细胞壁生物合成需要这些酶的证明将凸显以这些酶为目标开发抗真菌剂以治疗侵袭性念珠菌病和其他侵袭性真菌感染的可能性。