Supplements to Support Candida DNA Microarray Facilities

支持念珠菌 DNA 微阵列设施的补充剂

• 批准号: 6314824
• 负责人: Mira Edgerton
• 金额: $ 25万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-03-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6314824
• 关键词: Candida albicans; antifungal agents; calcium flux; calorimetry; candidiasis; cell membrane; chemical structure function; chemical substitution; circular dichroism; drug screening /evaluation; ergosterol; glycoproteins; high performance liquid chromatography; histidine; human tissue; intermolecular interaction; liposomes; membrane activity; membrane lipids; protein purification; protein structure function; protoplast /spheroplast; saliva; synthetic peptide; tissue /cell culture

DESCRIPTION (adapted from the Investigator's abstract): Incidence of oropharyngeal candidiasis has risen dramatically due to increased antibiotic usage and longer survival of individuals with compromised immune systems including patients on cancer chemotherapy, diabetics, AIDS patients and premature infants. Relatively few antifungal drugs are available for clinical treatment of oral or systemic candidiasis. Increased use of these agents to treat candidiasis in late stage AIDS and cancer patients has resulted in emergence of Candidal species with antifungal drug resistance, especially to azole-based drugs. Histatins (Hsts) are small cationic polypeptides produced by human major salivary glands. In vitro, Hst 5 is the most potent candidacidal member of the family which kills 90% to 100% of Candida species at physiological concentrations. Hsts' potent antifungal activity, lack of toxicity to humans and ability to kill azole-resistant yeast strains underscore the importance of detailed understanding of their mechanism of action. Improvements in candidacidal function of Hsts and development of oral Hst delivery systems also require information about the Hst-induced cascade of cellular events leading to C. albicans death. Previous studies showed that Hst mechanism of action is unique from other characterized antimycotic drugs in that induction of lethal effect is through a novel pathway initiated by ATP efflux from C. albicans cells, which occurs while the cell membrane is intact. Studies are proposed to examine related properties of Hst-induced ATP release, its cellular effects following Hst-induced ATP release leading to cell death, requirements for intracellular transport of Hst for candidacidal activity and examine potential involvement of cAMP, ABC transporters and purinergic receptors in C. albicans response to Hst 5. These studies will contribute to characterization of novel intracellular pathways utilized by Hst to cause yeast cell death and lead to further understanding of the role of ATP efflux as a cell regulatory or signaling process.

描述（改编自研究者的摘要）：发生率 由于抗生素的增加，口咽部念珠菌病急剧增加 免疫系统受损的个体的使用和更长的生存期 包括癌症化疗患者、糖尿病患者、艾滋病患者和 早产儿。可供临床使用的抗真菌药物相对较少 治疗口腔或全身念珠菌病。增加这些药物的使用 治疗晚期艾滋病和癌症患者的念珠菌病已取得成果 具有抗真菌药物耐药性的念珠菌物种的出现，尤其是 唑类药物。组氨酸 (Hsts) 是由以下物质产生的小阳离子多肽 人类主要唾液腺。在体外，Hst 5 是最有效的念珠菌 该家族的成员可杀死 90% 至 100% 的念珠菌物种 生理浓度。 Hsts 有效的抗真菌活性，缺乏 对人类的毒性和杀死唑类抗性酵母菌株的能力强调 详细了解其作用机制的重要性。 Hsts 念珠菌功能的改善和口腔 Hst 的发展 递送系统还需要有关 Hst 诱导的级联的信息 导致白色念珠菌死亡的细胞事件。先前的研究表明，Hst 其作用机制与其他抗真菌药物相比是独特的 致死效应的诱导是通过 ATP 启动的新途径 白色念珠菌细胞的流出，发生在细胞膜完整的情况下。 建议研究检查 Hst 诱导的 ATP 释放的相关特性， Hst 诱导 ATP 释放后的细胞效应导致细胞死亡， 念珠菌活性所需的 Hst 细胞内运输和 检查 cAMP、ABC 转运蛋白和嘌呤能的潜在参与 白色念珠菌中的受体对 Hst 5 的反应。这些研究将有助于 Hst 引起酵母菌的新型细胞内途径的表征 细胞死亡并导致进一步了解 ATP 外流作为细胞死亡的作用 细胞调节或信号传导过程。