BACTERIAL PROTEINASES IN PERIODONTAL DISEASE

牙周疾病中的细菌蛋白酶

• 批准号: 7089051
• 负责人: James Travis
• 金额: $ 24.53万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7089051
• 关键词: Bacteroides gingivalis; SDS polyacrylamide gel electrophoresis; bacteria infection mechanism; clinical research; complement; endopeptidases; enzyme activity; enzyme mechanism; fibrinolysis; flow cytometry; host organism interaction; human tissue; kallikreins; laboratory mouse; mass spectrometry; neutrophil; periodontitis; posttranslational modifications; protease inhibitor; tissue /cell culture; virulence

DESCRIPTION (provided by applicant): A primary organism involved in the development and progression of periodontal disease is the periodontopathogen, Porphyromonas gingivalis. This bacterium utilizes an arsenal of virulence factors to avoid host defense, allowing for its growth and proliferation at infected sites. Among these factors are proteolytic enzymes, which appear to be involved in the deregulation of cascade pathways, the inactivation of plasma proteinase inhibitors, and the disruption of chemotactic processes, all to the benefit of the invading organism. Many of these enzymes have been isolated and characterized in this laboratory, and it seems clear that inhibitors developed against them would significantly reduce the pathological symptoms associated with periodontitis. Nevertheless, in some types of periodontal disease, especially its early phase, other bacterial pathogens are likely to be involved. For these reasons, the Specific Aims of this project are as follows: 1) to expand the model we have developed which directly points to major roles for P. gingivalis proteinases in the pathological hallmarks of periodontal disease (bleeding on probing, swelling, tissue resorption, bone loss), 2), to initiate experiments to determine if other bacterial pathogens which are found at the early stages of periodontal disease also utilize proteolytic enzymes for host defense evasion, and 3) to screen for and purify low and high molecular weight proteinase inhibitors which may be synthesized by other oral organisms for the possible control of P. gingivalis growth and proliferation. Our long-term goals are to determine whether the mechanisms used by P. gingivalis to avoid host defense are a general process that other pathogens have adopted and to develop inhibitors against such enzymes in order to control or eradicate bacterial infections.

描述（由申请人提供）：牙周病的发生和发展涉及的主要微生物是牙周病原体，牙龈卟啉单胞菌。这种细菌利用一系列毒力因子来避免宿主防御，使其在感染部位生长和增殖。在这些因素中，蛋白水解酶似乎参与级联途径的失调、血浆蛋白酶抑制剂的失活和趋化过程的破坏，所有这些都有利于入侵生物体。这些酶中的许多已经在本实验室中分离和表征，并且似乎很明显，针对它们开发的抑制剂将显著减少与牙周炎相关的病理症状。然而，在某些类型的牙周疾病中，尤其是其早期阶段，可能涉及其他细菌病原体。因此，该项目的具体目标如下：1）扩展我们已经开发的模型，该模型直接指出牙龈卟啉单胞菌蛋白酶在牙周病的病理标志中的主要作用（探查出血、肿胀、组织吸收、骨丢失），2），启动实验以确定在牙周病早期发现的其他细菌病原体是否也利用蛋白水解酶进行宿主防御逃避，和3）筛选和纯化低和高分子量蛋白酶抑制剂，所述蛋白酶抑制剂可由其它口腔生物体合成，用于可能控制牙龈卟啉单胞菌生长和增殖。我们的长期目标是确定牙龈卟啉单胞菌避免宿主防御的机制是否是其他病原体所采用的一般过程，并开发针对此类酶的抑制剂以控制或根除细菌感染。