Molecular Aspects of Oral Plaque Formation

口腔菌斑形成的分子方面

• 批准号: 7568859
• 负责人: Richard J Lamont
• 金额: $ 35.47万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7568859
• 关键词: Address; Adherence; Adhesions; Adhesives; Amino Acids; Anaerobic Bacteria; Bacteria; Bacterial Adhesins; Bacterial Infections; Binding; Biological Assay; Cell Communication; Cells; Characteristics; Communication; Communities; Community Developments; Complex; DNA-Binding Proteins; Dental Plaque; Detection; Development; Disease; Down-Regulation; Electrostatics; Event; Family; Fostering; Genes; Goals; Human; Individual; Knowledge; Life Style; Mediating; Membrane Proteins; Microbial Biofilms; Minor; Molecular; Oral cavity; Organism; Peptides; Periodontal Diseases; Physiological; Porphyromonas gingivalis; Process; Property; Protein Subunits; Protein Tyrosine Phosphatase; Proteins; Proteomics; Public Health; Role; Severities; Shapes; Signal Pathway; Signal Transduction; Signaling Molecule; Site-Directed Mutagenesis; Social Behavior; Specificity; Staging; Stimulus; Streptococcus gordonii; Structure; Surface; System; Therapeutic; Therapeutic Intervention; Tooth structure; Toothpaste; Transcriptional Regulation; Translating; base; fimbria; inhibitor/antagonist; microbial community; oral plaque; oral streptococci; pathogen; prevent; receptor; tooth surface; transcriptomics

DESCRIPTION (provided by applicant): Dental plaque develops as a complex, multispecies biofilm on the tooth surface and is a direct precursor of periodontal diseases, one of the most common bacterial infections of humans. The general principles of plaque biofilm development and transition from a commensal to a pathogenic entity are established. Pioneer colonizers such as oral streptococci first attach and accumulated on the tooth surface. Through a variety of adhesive, signaling and physiologic interactions, these early colonizers then foster the colonization of later arrivals, including potential pathogens such as P. gingivalis. Our ongoing studies address the stage of biofilm development involving initial attachment of planktonic cells of P. gingivalis to a substratum of S. gordonii, transition of P. gingivalis to a biofilm lifestyle, and development of an architecturally distinct heterotypic biofilm. Adhesion of P. gingivalis to S. gordonii is mediated by the long and short fimbriae of P. gingivalis that interact with streptococcal GAPDH and Ssp surface proteins. Within SspB, the amino acids in an adhesive domain spanning residues 1167-1193, designated BAR, dictate binding activity and specificity. The interaction of SspB with the short fimbrial subunit protein, Mfa, induces a distinct transcriptional profile within P. gingivalis that provides the impetus for subsequent accumulation of a mixed species biofilm. One such regulated gene, ptpA, encodes a tyrosine phosphatase that participates in a control mechanism to optimize the size of the heterotypic biofilm community. Longer term adaptation to the community lifestyle causes P. gingivalis to downregulate expression of Mfa. The objectives of this application are to characterize the SspB-Mfa interacting interface; to define the role of the P. gingivalis tyrosine phosphatase PtpA in regulatory networks that control heterotypic biofilm development with S. gordonii; and to characterize the transcriptional regulation of mfa expression. We shall utilize global approaches such as transcriptomics and proteomics in combination with targeted approaches such as site specific mutagenesis, protein-protein and protein-DNA binding assays, to define and dissect the functions of individual biofilm effector molecules and to reveal the hierarchical network structure that controls heterotypic biofilm development. Public Health Significance: Of relevance to public health is the potential to translate this knowledge into the development of toothpastes or mouthrinses that contain inhibitors of the process of P. gingivalis build-up on the teeth. These would reduce the ability of P. gingivalis to persist in the mouth and consequently prevent or reduce the severity of gum disease caused by this organism.

描述（由申请人提供）：牙菌斑在牙齿表面形成复杂的多物种生物膜，是牙周病的直接前兆，牙周病是人类最常见的细菌感染之一。建立了斑块生物膜发育和从共生实体向致病实体转变的一般原理。口腔链球菌等先锋定植菌首先附着并积聚在牙齿表面。通过各种粘附、信号传导和生理相互作用，这些早期定殖者随后促进后来到达的定殖者的定殖，包括潜在的病原体，例如牙龈卟啉单胞菌。我们正在进行的研究涉及生物膜发育阶段，包括牙龈卟啉单胞菌浮游细胞最初附着到戈氏链球菌基质、牙龈卟啉单胞菌向生物膜生活方式的转变以及结构上独特的异型生物膜的发育。牙龈卟啉单胞菌与戈氏链球菌的粘附是由牙龈卟啉单胞菌的长菌毛和短菌毛与链球菌 GAPDH 和 Ssp 表面蛋白相互作用介导的。在 SspB 内，跨越残基 1167-1193 的粘附结构域中的氨基酸（称为 BAR）决定了结合活性和特异性。 SspB 与短菌毛亚基蛋白 Mfa 的相互作用在牙龈卟啉单胞菌内诱导独特的转录谱，为随后混合物种生物膜的积累提供动力。一种这样的调节基因 ptpA 编码一种酪氨酸磷酸酶，该酶参与控制机制以优化异型生物膜群落的大小。对社区生活方式的长期适应导致牙龈卟啉单胞菌下调 Mfa 的表达。该应用的目标是表征 SspB-Mfa 交互接口；确定牙龈卟啉单胞菌酪氨酸磷酸酶 PtpA 在控制戈氏链球菌异型生物膜发育的调控网络中的作用；并表征 mfa 表达的转录调控。我们将利用转录组学和蛋白质组学等全局方法，结合位点特异性诱变、蛋白质-蛋白质和蛋白质-DNA结合测定等靶向方法，来定义和剖析单个生物膜效应分子的功能，并揭示生物膜效应分子的分层网络结构。控制异型生物膜的发育。公共卫生意义：与公共卫生相关的是，有可能将这些知识转化为牙膏或漱口水的开发，这些牙膏或漱口水含有牙龈卟啉单胞菌在牙齿上积聚过程的抑制剂。这些将降低牙龈卟啉单胞菌在口腔中持续存在的能力，从而预防或减轻由该生物体引起的牙龈疾病的严重程度。