ORAL ANTIFUNGAL NATURAL AND SYNTHETIC HISTIDINE PEPTIDES

白色念珠菌是一种机会酵母菌，是最常见的 在口腔中遇到的最重要的真菌病原体。 因为 对C知之甚少。白念珠菌宿主相互作用，该提案 被设计来研究那些可能 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 在这项建议中使用，以集中在一组组氨酸丰富的 人类唾液中独特存在的多肽。 近期体外试验 我们实验室的证据促使我们假设 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至关重要。 假设，并确定组氨酸及其组分的关键作用 咪唑基团的抗真菌活性。 为了帮助 确定这些天然的生理浓度是否 分泌的分子在C.白念珠菌病，体内口服 从念珠菌病患者获得的分离物， 实验室菌株C.将对白色念珠菌进行体外试验， 对唾液中富含组氨酸的多肽和合成的 同源组氨酸肽。 抗菌药物敏感性测试将 包括生长抑制浊度测量和菌落 形成单位活力测定。 此外，天然和 将评估合成组氨酸肽对芽管形成的影响。 一个 使用义齿性口炎患者体内临床模型系统将 开发的信息获取的敏感性C。中白色 它的天然口腔环境的组氨酸肽。 的能力 组氨酸肽抑制C.白色念珠菌在 将检查义齿丙烯酸表面，并与念珠菌抑制剂 对相应的C.体内白色念珠菌 每一个病人的分离。 研究也将在 超微结构水平，以深入了解分子机制， 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.