HISTIDINE-RICH POLYPEPTIDES, ORAL CANDIDIASIS AND AIDS

白色念珠菌和机会性酵母菌，通常存在于口腔中， 微生物植物群的无害成员，是最常见的 在口腔中遇到的最重要的真菌病原体。 艾滋病毒 感染的个体，获得口腔念珠菌病已成为一个早期 机会性感染和艾滋病发展的指标。 在 目前，人们对C的转变知之甚少。白色念珠菌病 寄生 理解这种从正常人到患病者的转变 关于C的规定。口腔内的白色念珠菌 非免疫性天然宿主防御因子代表了 这项研究。 我们的具体目标将集中在家庭的 唾液富含组氨酸的多肽（HRPs），我们认为它是 口腔的天然抗真菌剂。 在体外和体内 研究将用于完成以下任务：1）确定 六个主要HRPs的结构。 纯化及 腮腺唾液中HRP的表征将通过HPLC实现， 随后进行氨基酸气相测序。 结构将得到确认 通过与化学合成肽的比较。 2)确定 这六种主要HRP的次要分解肽的结构。 的 将评估腮腺唾液蛋白水解酶的特异性 通过阳离子聚丙烯酰胺基因电泳、HPLC分析， 氨基酸测序 3)确定主要成分的浓度， 正常健康个体腮腺唾液中的少量HRPs。 HPLC和 将使用免疫测定来定量HRP。 4)确定 HRPs和腮腺的生理浓度的抗真菌效力 唾液对C.白色念珠菌 抗菌药物敏感性测试将 包括芽生孢子集落形成单位活力和芽管 发育分析。 5)确定HRPs是否能杀死C。白色念珠菌和 在义齿丙烯酸表面生长的其他酵母菌。 临床 使用义齿性口炎患者的模型系统已经从 测试HRP在体内水平的抗真菌作用。 六、 探讨HRPs与艾滋病、口腔念珠菌病的关系。 HIV感染者的腮腺唾液，有和没有口服 将分析念珠菌病的HRP和抗真菌效力。 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.