HISTIDINE-RICH POLYPEPTIDES, ORAL CANDIDIASIS AND AIDS

白色念珠菌和机会酵母，通常以口腔中的形式存在 是微生物区系中一种无害的成员，是最常见的 口腔中遇到也是最重要的真菌病原体。在艾滋病中 感染者中，口腔念珠菌病的获得者已成为早期 机会性感染和艾滋病发展的指标。在… 目前，人们对白念珠菌的共生关系转变为 寄生。理解这种从正常人到病人的转变 与口腔内白色念珠菌的调节有关的状态 非免疫性自然宿主防御因子代表了猪瘟的长期目标 这项研究。我们的具体目标将集中在 唾液富含组氨酸多肽(HRPs)被我们认为是 口腔中的天然抗真菌药剂。无论是体外还是体内 研究将用于完成以下工作：1)确定 六个主要人力资源计划中每一个的结构。净化和 从腮腺唾液中提取的高密度脂蛋白将通过高效液相色谱进行表征， 然后进行氨基酸气相测序。结构将得到确认 通过与化学合成的多肽进行比较。2)确定 这六个主要HRP的次要破碎肽的结构。这个 腮腺唾液蛋白水解酶的特异性将被评估 通过阳离子聚丙烯酰胺凝胶电泳法、高效液相色谱仪和 氨基酸测序。3)确定主要污染物的浓度和 正常健康人腮腺唾液中的微量HRPs。高效液相色谱仪和 将使用免疫测定法对HRP进行定量。4)确定 人参皂苷和腮腺生理浓度的抗真菌活性 唾液抗白色念珠菌。抗菌药物敏感性测试将 包括芽孢子集落形成单位活力和芽管 发展分析。5)确定HRP是否可以杀死白色念珠菌和 生长在假牙表面的其他酵母菌。一家诊所 使用义齿口炎患者的模型系统已经从 在体内水平上测试HRPS的抗真菌作用。6) 确定艾滋病、口腔念珠菌病与HRPs之间的关系。 有口腔和无口腔HIV感染者的腮腺唾液 将对念珠菌病进行HRP和抗真菌效力分析。它 假设预防口腔念珠菌病可能导致 预防机会性感染和艾滋病的发展。

Candida albicans, and opportunistic yeast, normally present in the mouth as a harmless member of the microbial flora, is the most frequently encountered and most important fungal pathogen in the oral cavity. In HIV infected individuals, acquisition of oral candidiasis has become an early indicator of the development of opportunistic infections and AIDS. At present, little is known about the shift from C. albicans commensalism to parasitism. An understanding of this shift form the normal to the diseased state in relation to the regulation of C. albicans in the oral cavity by nonimmune natural host defense factors represents the long term goal of this research. Our specific aims will focus upon the family of the salivary histidine-rich polypeptides (HRPs) which are thought by us to be the natural antifungal agents of the mouth. Both in vitro and in vivo studies will be used to accomplish the following: 1) Determine the structures of each of the six major HRPs. Purification and characterization of the HRPs from parotid saliva will be achieved by HPLC, followed by amino acid gas phase sequencing. Structures will be confirmed through comparison to chemically synthesized peptides. 2) Determine the structures of the minor breakdown peptides of these six major HRPs. The specificity of parotid salivary proteolytic enzymes will be assessed through cationic polyacrylamide gen electrophoresis, HPLC analysis and amino acid sequencing. 3) Determine the concentration of the major and minor HRPs in the parotid salivas of normal healthy individuals. HPLC and immuno-assays will be used to quantitate the HRPs. 4) Determine the antifungal potency of physiological concentrations of the HRPs and parotid saliva against C. albicans. Antimicrobial susceptibility testing will include both blastospore colony forming unit viability and germ tube development assays. 5) Determine whether the HRPs can kill C. albicans and other yeast species growing on the denture acrylic surface. A clinical model system employing denture stomatitis patients has been developed from testing the antifungal effects of the HRPs at the in vivo level. 6) Determine the relationship between AIDS, oral candidiasis and the HRPs. Parotid salivas of HIV-infected individual with and without oral candidiasis will be analyzed for the HRPs and for antifungal potency. It is hypothesized that the prevention of oral candidiasis may lead to the prevention of the development of opportunistic infections and AIDS.