Regulation of Porphyromonas gingivalis gene expression

慢性牙周炎(牙周病)是一种与细菌相关的牙齿支持组织的慢性炎症性疾病，会导致牙齿支持的破坏，并最终导致牙齿脱落。这种疾病是一个重大的公共卫生问题，具有巨大的经济负担，并与心血管疾病风险增加有关。牙龈卟啉单胞菌被认为是慢性牙周炎发生发展的主要致病菌。这种细菌是龈下牙菌斑的一部分，牙菌斑是附着在牙周线以下牙齿表面的一种生物膜，它会释放一系列蛋白质和细胞毒剂，通过宿主免疫反应的失调直接或间接地对牙齿的支持组织造成损害。为了引起疾病，这种细菌必须能够作为生物膜生长，并经受住宿主的免疫反应。详细了解这种细菌如何能够在龈下菌斑中建立和繁殖，耐受作为免疫反应一部分的氧化攻击和高温，并获得必要的微量营养素铁，将为开发特定的抑制剂提供新的靶点，这些抑制剂可能作为控制慢性牙周炎的辅助治疗手段。我们将使用最先进的DNA微阵列分析来确定调节与这种细菌毒力相关的基因的蛋白质。我们从这项研究中获得的见解将在理解人类疾病方面有更广泛的应用，这些疾病是由细菌在人体不同表面作为生物膜生长引起的。

Chronic periodontitis (gum disease) is a chronic inflammatory disease of the supporting tissues of the teeth associated with bacteria that results in the destruction of tooth support and can ultimately lead 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. The bacterium Porphyromonas gingivalis is recognized as the major causative pathogen in the development of chronic periodontitis. This bacterium is part of subgingival dental plaque, a biofilm attached to the surface of the tooth below the gum line, and releases a range of proteins and cytotoxic agents that cause damage to the tooth's supporting tissues both directly and indirectly through the dysregulation of the host's immune response. To cause disease this bacterium must be able to grow as a biofilm and withstand the immune response of the host. Detailed knowledge of how this bacterium is able to establish and proliferate in subgingival plaque, tolerate the oxidative attack and elevated temperatures that are part of the immune response and obtain the essential micronutrient iron will provide new targets for the development of specific inhibitors that may have utility as an adjunctive therapeutic for the control of chronic periodontitis. We will use a state of the art DNA microarray analysis to determine the proteins that regulate genes associated with the virulence of this bacterium. The insights we gain from this study will have broader application for the understanding of human disease that is caused by bacteria that grow as biofilms on various surfaces of the human body.