Molecular characterization of the gingipains of Porphyromonas gingivalis

慢性牙周炎是一种与细菌相关的牙齿支持组织的炎症性疾病，其导致牙齿支持的破坏并最终导致牙齿脱落。该疾病是一个重大的公共卫生问题，具有巨大的经济负担，并与心血管疾病和早产和低出生体重的风险增加有关。牙龈卟啉单胞菌（Porphyromonas gingivalis）是引起慢性牙周炎的主要致病菌。我们已经鉴定出牙龈卟啉单胞菌的主要毒力因子，其是参与结合和破坏宿主蛋白的蛋白质的胞外复合物。该提案的目的是使用最先进的蛋白质组学技术表征细胞表面复合物的分泌、分子加工和组装。这项研究将提供有价值的深入了解细菌病原体的分子过程，导致毒力。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异性抑制剂提供分子靶点，所述特异性抑制剂可能具有作为预防性治疗剂和/或作为控制慢性牙周炎的预防方案或维持方案的一部分的效用。此外，从这项研究中得到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。

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.