P GINGIVALIS HSP90 RECOGNITION IN PERIODONTAL DISEASE

P GINGIVALIS HSP90 在牙周疾病中的识别

• 批准号: 2836661
• 负责人: DOMENICA Giovanna SWEIER
• 金额: $ 8.06万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2836661
• 关键词: Actinobacillus actinomycetemcomitans; Bacteroides gingivalis; antibody titering; bacteria infection mechanism; bacterial genetics; bacterial proteins; epitope mapping; gene expression; host organism interaction; human tissue; mutant; nucleic acid probes; pathologic process; periodontium disorder; polymerase chain reaction; protein structure function; stress proteins; virulence

This proposal is submitted as part of the application for a Research Career Award for Domenica G. Sweier, D.D.S. A Research Career Award will enable the applicant to complete her graduate dentist scientist training in the Oral Health Sciences Ph.D. Program at the University of Michigan School of Dentistry. The objective of this proposal is to investigate the role of the P. gingivalis Hsp90 homologue in the pathogenesis of the microorganism in periodontal disease. Heat shock proteins have been found to be important in many soft tissue infections and have been referred to as virulence factors in some models. For example, the overexpression of Saccharomyces cerevisiae Hsp90 enhances the virulence of this organism in mice (Hodgetts et al., 1996). In humans, anti-Hsp90 seroconversion is associated with a higher survival rate in systemic candidiasis. Moreover, in candidiasis, antibodies to a specific conserved epitope were shown to confer protection (Matthews et al., 1995). Heat shock proteins have also been implicated in adherence mechanisms. A 66kDa Hsp of Salmonella typhimurium is believed to be responsible for binding to the intestinal mucosa and is considered a virulence factor in this microorganism (Ensgraber and Loos, 1992). Elevated levels of serum antibodies to purified human Hsp90 in healthy adults were associated with periodontal health (manuscript in preparation). Healthy individuals had higher anti-Hsp90 serum antibodies than those individuals diagnosed with periodontal disease. Additionally, the P. gingivalis Hsp90 homologue has been found to cross-react with anti-human Hsp90 stress protein antibodies. We feel that further studies on the role of the Hsp90 homologue of P. gingivalis in host-bacteria interactions in periodontal disease will result in the development of new diagnostic and therapeutic modalities. The studies proposed in this application will address the following global hypothesis: Specific epitopes of the Porphyromonas gingivalis Hsp90 homologue are putative virulence determinants that may be blocked by antibodies in sera of healthy subjects. In order to begin to address this hypothesis, we proposed to: (1) clone and characterize the P. gingivalis hsp90 gene homologue, (2) express the P. gingivalis hsp90 gene homologue and harvest the protein, and (3) map the immunodominant epitopes recognized in health and disease.

该提案作为Domenica G. Sweier，D.D.S。的研究职业奖的一部分提交。 研究职业奖将使申请人能够在口腔健康科学博士学位上完成她的研究生牙医科学家培训。密歇根大学牙科学院的计划。该提案的目的是研究牙龈疟原虫Hsp90同源物在牙周疾病中微生物发病机理中的作用。 在许多软组织感染中发现热休克蛋白很重要，并且在某些模型中被称为毒力因子。 例如，酿酒酵母HSP90的过表达增强了这种生物在小鼠中的毒力（Hodgetts等，1996）。 在人类中，抗HSP90血清转化与全身性念珠菌病的生存率更高有关。 此外，在念珠菌病中，对特定保守表位的抗体被证明可以赋予保护（Matthews等，1995）。 热休克蛋白也与粘附机制有关。 据信，鼠伤寒沙门氏菌的66kDa HSP被认为是与肠粘膜结合的原因，被认为是这种微生物中的毒力因子（Ensgraber and Loos，1992）。健康成年人中纯化的人类HSP90的血清抗体水平升高与牙周健康有关（制备中的手稿）。 健康个体的抗HSP90血清抗体高于诊断患有牙周疾病的人。 此外，已经发现牙龈疟原虫HSP90同源物与抗人HSP90应激蛋白抗体交叉反应。 我们认为，关于牙龈疟原虫在牙周疾病中HSP90同源物在宿主 - 细菌相互作用中的作用的进一步研究将导致新的诊断和治疗方式的发展。本应用程序中提出的研究将解决以下全球假设：牙卟啉单胞菌HSP90同源物的特定表位是假定的毒力决定因素，这些决定因素可能会被健康受试者血清中的抗体阻止。 为了开始解决这一假设，我们提出了：（1）克隆并表征牙龈疟原虫HSP90基因同源物，（2）表达牙龈疟原虫HSP90基因同源物并收获蛋白质，以及（3）映射免疫适度的表现在健康和疾病中。