Molecular characterization of the gingipains of Porphyromonas gingivalis

牙龈卟啉单胞菌牙龈蛋白酶的分子特征

• 批准号: nhmrc : 350427
• 负责人: Dr Nada Slakeski
• 金额: $ 26.27万
• 依托单位: The University of Melbourne
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2005
• 资助国家: 澳大利亚
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/molecular-characterization-gingipains-porphyromonas-gingivalis/83106
• 关键词: Molecular; characterization; gingipains; Porphyromonas; gingivalis

Chronic periodontitis is a bacteria-associated inflammatory disease of the supporting tissues of the teeth, which results in the destruction of tooth support and ultimately leads to tooth loss. The disease is a major public health problem with a large economic burden and has been associated with an increased risk of cardiovascular disease and pre-term birth and low birth weight. The bacterium Porphyromonas gingivalis has now been identified as a major pathogen in the development of chronic periodontitis. We have identified a major virulence factor of P. gingivalis which is an extracellular complex of proteins involved in binding and destroying host proteins. The aim of this proposal is to characterize the secretion, molecular processing and assembly of the cell surface complex using state-of-the-art proteomic techniques. This study will provide valuable insight into the molecular processes of a bacterial pathogen that leads to virulence. Detailed knowledge on the unique molecular events involved in secretion, processing and assembly of a major virulence factor will provide molecular targets for the development of specific inhibitors that may have utility as an adjunctive therapeutic and-or as part of a preventive regime or maintenance program for the control of chronic periodontitis. Further, the molecular insight that will result from this study will have broader application in the understanding of virulence factor processing of a Gram-negative pathogen that will provide paradigms for other bacterial pathogens.

慢性牙周炎是一种与细菌相关的牙齿支持组织炎症性疾病，导致牙齿支持破坏，最终导致牙齿脱落。该疾病是一个重大的公共卫生问题，造成巨大的经济负担，并与心血管疾病、早产和低出生体重的风险增加有关。牙龈卟啉单胞菌现已被确定为慢性牙周炎发展的主要病原体。我们已经确定了牙龈卟啉单胞菌的主要毒力因子，它是参与结合和破坏宿主蛋白质的细胞外蛋白质复合物。该提案的目的是利用最先进的蛋白质组学技术来表征细胞表面复合物的分泌、分子加工和组装。这项研究将为了解导致毒力的细菌病原体的分子过程提供有价值的见解。对主要毒力因子的分泌、加工和组装所涉及的独特分子事件的详细了解将为开发特定抑制剂提供分子靶标，这些抑制剂可用作辅助治疗和/或作为控制慢性牙周炎的预防方案或维持计划的一部分。此外，这项研究产生的分子见解将在理解革兰氏阴性病原体的毒力因子加工方面具有更广泛的应用，这将为其他细菌病原体提供范例。