Regulation of Porphyromonas gingivalis gene expression
Regulation of Porphyromonas gingivalis gene expression
批准号:
nhmrc : 454618
负责人:
A/Pr John Boyce
金额:
$35.45万
依托单位国家:
澳大利亚
项目类别:
NHMRC Project Grants
财政年份:
2007
资助国家:
澳大利亚
项目状态:
已结题
起止时间:
2007-01-01 至 2009-12-31
中文摘要
慢性牙周炎(牙龈疾病)是一种与细菌相关的牙齿支撑组织慢性炎症性疾病,会导致牙齿支撑破坏,最终导致牙齿脱落。该疾病是一个重大的公共卫生问题,具有巨大的经济负担,并与心血管疾病风险增加有关。牙龈卟啉单胞菌是引起慢性牙周炎的主要致病菌。这种细菌是龈下牙菌斑的一部分,生物膜附着在牙龈线以下的牙齿表面,并释放一系列蛋白质和细胞毒性剂,通过宿主免疫反应的失调直接和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承受宿主的免疫反应。详细了解这种细菌是如何能够建立和增殖的龈下菌斑,耐受氧化攻击和升高的温度,是免疫反应的一部分,并获得必需的微量营养素铁将提供新的目标,为特定的抑制剂,可能有效用作为慢性牙周炎的控制预防性治疗的发展。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的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更广泛地应用于理解由细菌引起的人类疾病,这些细菌在人体的各种表面上生长为生物膜。
英文摘要
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.
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