Tight Adherence Genes of a Periodontal Pathogen

牙周病原体的紧密粘附基因

• 批准号: 6649294
• 负责人: DAVID H FIGURSKI
• 金额: $ 38.87万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6649294
• 关键词: Actinobacillus actinomycetemcomitans; RNase protection assay; affinity chromatography; autoradiography; bacteria infection mechanism; bacterial genetics; bacterial proteins; cell aggregation; complementary DNA; gene expression; genetic mapping; genetic promoter element; genetic regulation; immunoprecipitation; infection; molecular cloning; molecular film; northern blottings; operon; periodontitis; polymerase chain reaction; protein localization; protein protein interaction; protein structure function; tooth surface; western blottings

DESCRIPTION (provided by applicant): The Gram-negative bacterium, Actinobacillus actinomycetemcomitans, is believed to be the etiologic agent for localized juvenile periodontitis (LJP), a particularly destructive disease in adolescents. The incidence of LJP varies among demographic groups and disproportionately burdens minorities and the poor. A. actinomycetemcomitans has been associated with a variety of other infections, notably brain abscesses, and it is a member of the clinically important HACEK group of bacteria implicated in infective endocarditis. A striking characteristic of fresh clinical isolates of A. actinomycetemcomitans is their ability to form extremely tenacious biofilms, a property thought to be critical for colonization of teeth and other surfaces. Molecular genetic studies in this laboratory have revealed that the genome of A. actinomycetemcomitans maintains a cluster of tad genes required for tight adherence to surfaces. The studies indicate that the tad genes are part of a locus of 14 genes encoding a novel secretion system for the assembly and release of long, bundled FIp fibrils and that the fibrils are required for tight nonspecific adherence to surfaces and bacterial autoaggregation. Remarkably similar tad-like loci were subsequently found in the genome sequences of a wide variety of Gram-negative and Gram-positive Bacteria, including many significant pathogens, and in Archaea. Given the clear requirement of the tad gene cluster for adherence of A. actinomycetemcomitans, the tad loci in other organisms are likely to be important for microbial colonization in a variety of environmental niches. Proposed here are molecular and genetic studies of the tad locus of A. actinomycetemcomitans. The objectives are the following: 1) to understand the mechanisms of expression and regulation of the genes of the tad locus; and 2) to determine the locations, interactions, and molecular functions of the gene products in secretion and fibril assembly. These studies are expected to lead to a basic understanding of a novel secretion system of bacteria and its role in the biogenesis of fibrils required for tight adherence and colonization by A. actinomycetemcomitans. Since of the widespread nature of the tad loci, these studies should also lead to new insights into colonization by other bacterial pathogens and may serve to identify new targets for development of antibiotics.

描述（由申请人提供）：革兰氏阴性细菌，放线肌肌动症，被认为是局部少年牙周炎（LJP）的病因学剂，这是青少年中特别具有破坏性的疾病。 LJP的发病率在人口群体之间有所不同，而少数群体和穷人负担不成比例。 A.放线症患者与其他多种感染（尤其是脑脓肿）有关，它是与感染性心内膜炎有关的临床上重要的Hacek细菌组的成员。 曲霉曲霉曲霉的新鲜临床分离株的惊人特征是它们形成极度顽强的生物膜的能力，这是一种被认为对牙齿和其他表面定植至关重要的特性。该实验室中的分子遗传研究表明，放线杆菌的基因组保持了紧密粘附到表面所需的一群TAD基因。研究表明，TAD基因是编码新型分泌系统的14个基因的一部分，用于组装和释放长，捆绑的FIP原纤维，而原纤维是非特异性非特异性粘附到表面和细菌自身聚集的紧密粘附所必需的。随后在各种革兰氏阴性菌和革兰氏阳性细菌的基因组序列中发现了非常相似的TAD样基因座，包括许多重要的病原体和古细菌。鉴于TAD基因簇对粘膜曲霉的依从性的明确要求，其他生物体的TAD基因座对于多种环境壁ches中的微生物定植可能很重要。 此处提出的是曲霉曲霉曲霉的TAD基因座的分子和遗传研究。目标是：1）了解TAD基因座基因的表达和调节的机理； 2）确定分泌和原纤维组装中基因产物的位置，相互作用和分子功能。预计这些研究将导致对细菌的新分泌系统的基本理解及其在A. statomysycetemcomentans粘附和定殖所需的原纤维生物发生中的作用。由于TAD基因座的广泛性质，这些研究也应导致其他细菌病原体对定殖的新见解，并可能有助于确定开发抗生素的新靶标。