IMMUNODOMINANT STRESS PROTEINS OF P GINGIVALIS

微生物在感染过程中产生新的蛋白质。 这些蛋白质中的许多的表达代表了对压力的响应 由宿主（应激蛋白，HSP）施加，并且对 微生物追求感染过程的能力。 保卫 宿主通常依赖于这些蛋白质免疫识别。 本申请中提供的初步数据表明， 一种这样的蛋白质，HSP 90，与牙龈健康和 牙龈卟啉单胞菌（Porphyromonas gingivalis）的低水平定植， 牙周病原体 关于应激蛋白的数据很少 牙周病病原体。 应激蛋白是免疫显性的， 其他非口腔细菌感染中的重要抗原。 调查 牙周病原体的应激蛋白可能对我们的 了解牙周病的病因。 本实验室的长期目标是确定压力的作用 蛋白质在牙周病的过程中，通过调查他们的 表达、调节以及与宿主防御机制的相互作用。 的 如本提案所述，第一步是表征90 kD 牙龈卟啉单胞菌的应激蛋白，根据我们的初步研究， 在牙周病中起重要作用。 具体 本文拟验证的假设是：HSP 90由P. 在模拟感染过程的条件下，牙龈炎。 表达 牙龈卟啉单胞菌HSP 90的表达与其毒力和抗体水平有关 针对牙龈卟啉单胞菌的HSP 90是保护性的。 我们建议测试 这一假设通过：（1）表征的条件下，P。 牙龈卟啉单胞菌HSP 90的表达; 牙龈组织HSP 90基因的表达;（3）免疫电镜观察 将HSP 90蛋白定位在牙龈卟啉单胞菌的表面和内部 （4）研究HSP 90对P. 牙龈炎的两种动物模型。

Microorganisms produce new proteins during the infectious process. Expression of many of these proteins represents the response to stresses imposed by the host (stress-proteins, HSP) and is important to the microorganism's ability to pursue the infectious process. Defense of the host is often dependent on immunologic recognition of these proteins. Preliminary data presented in this application shows that humoral immunity to one such protein, HSP90, is associated with both gingival health and low level colonization by Porphyromonas gingivalis, one of the principal periodontal pathogens. There is a paucity of data on the stress proteins of the periodontal pathogens. The stress proteins are immunodominant and important antigens in other non-oral bacterial infections. Investigations of the stress proteins of periodontal pathogens may be crucial to our understanding of the etiology of periodontal disease. The long-term goals of this laboratory are to define the role(s) of stress proteins in the periodontal disease process by investigating their expression, regulation and interaction with host defense mechanisms. The first step, as outlined in this proposal, is to characterize the 90 kD stress protein of P. gingivalis which, based on our preliminary studies, is important in the organism's role in periodontal disease. The specific hypothesis to be tested in this proposal is: HSP90 is expressed by P. gingivalis during conditions that mimic the infectious process. Express of HSP90 by P. gingivalis contributes to its virulence and antibodies directed against P. gingivalis HSP90 are protective. We propose to test this hypothesis by: (1) characterizing the conditions under which P. gingivalis HSP90 is expressed; (2) cloning and sequencing the P. gingivalis HSP90 gene; (3) performing immuno electronmicroscopic studies to localize the HSP90 protein on the surface and inside the P. gingivalis cell; (4) evaluating the contribution HSP90 to the virulence of P. gingivalis in two animal models.