ORAL ANTIFUNGAL NATURAL AND SYNTHETIC HISTIDINE PEPTIDES

白色念珠菌是最常见的一种机会主义酵母菌 口腔中遇到也是最重要的真菌病原体。因为 对白念珠菌与宿主的相互作用知之甚少，这项提议 被设计用来研究那些可能会 参与慢性和急性口腔疾病的调控 念珠菌病。特别是，基础和临床研究应 在这个提案中用来关注一群富含组氨酸的 人类唾液中独有的多肽。最近的体外试验 我们实验室的证据促使我们推测一种抗真菌药物 这些唾液中富含组氨酸的多肽在口腔中的作用。 然而，这里概述的详细研究对于发展这一点是必不可少的。 假设和确定组氨酸及其成分的关键作用 建议咪唑基团具有抗真菌活性。为了帮助一个 测定这些天然物质的生理浓度 分泌分子在白念珠菌疾病中发挥作用，无论是在体内还是在口服中 从念珠菌病患者中获得并可从商业上获得的分离株 白念珠菌实验室菌株将在体外进行检测 对唾液富含组氨酸的多肽和人工合成的易感性 同源组氨酸多肽。抗菌药物敏感性测试将 包括生长抑制比浊法测量和菌落 形成单位存活率测定。此外，自然和自然的影响 将评估合成组氨酸肽对胚管形成的影响。一个 使用义齿口炎患者的体内临床模型系统将被 开发以获取关于白念珠菌敏感性的信息 其天然的口腔环境中含有组氨酸多肽。美国人的能力 组氨酸多肽对白念珠菌生长的抑制和杀灭作用 对义齿表面的亚克力进行检查，并与假牙进行比较 体内对相应白色念珠菌的杀灭活性 每个病人的分离物。研究也将在 在超微结构水平上深入了解黄体生成素的分子机制 天然和合成组氨酸肽的抗真菌作用。

Candida albicans, an opportunistic yeast, is the most frequently encountered and most important fungal pathogen in the oral cavity. Because so little is known about C. albicans-host interactions, this proposal has been designed to investigate those natural host defense factors which might be involved in the regulation and control of chronic and acute oral candidiasis. In particular, basic and clinical research studies shall be utilized in this proposal to focus upon a group of histidine-rich polypeptides which are uniquely present in human saliva. Recent in vitro evidence from our laboratory has promoted us to hypothesize an antifungal role for these salivary histidine-rich polypeptides in the oral cavity. However, detailed studies outlined here are essential to develop this hypothesis and to establish the key role of histidine with its constituent imidazole group in the proposed antifungal activity. In order to aid in a determination of whether physiological concentrations of these naturally secreted molecules play a role in C. albicans disease, both in vivo oral isolates obtained from candidiasis patients and commercially available laboratory strains of C. albicans will be tested for their in vitro susceptibility to the salivary histidine-rich polypeptides and to synthetic homologous histidine peptides. Antimicrobial susceptibility testing will include both growth inhibitory turbidimetric measurements and colony forming unit viability assays. In addition, the effect of natural and synthetic histidine peptides on germ tube formation will be assessed. An in vivo clinical model system employing denture stomatitis patients will be developed to acquire information on the susceptibility of C. albicans in its native oral environment to the histidine peptides. The ability of the histidine peptides to inhibit the growth of and kill C. albicans on the denture acrylic surface will be examined and compared to the candidastatic and candidacidal activities against the corresponding C. albicans in vivo isolates of each patient. Studies will also be initiated at the ultrastructural level to gain insight into the molecular mechanism of antifungal action of the natural and synthetic histidine peptides.