GENETIC ANALYSIS--ADHESION OF S SANGUIS TO S PELLICLE

这项提案的总体目标是描述 副血链球菌FW213菌毛粘附素(FIMA) 分子水平。这种蛋白质在整个生命周期中高度保守 血链球菌，已被证明是一种粘附素在at 血吸虫的四个遗传组中至少有两个是 随后致病物种的增加。来自多个国家的数据 实验室强烈表明，生态演替发生在 牙菌斑的形成和发展，以及血液 (Sa)似乎由几种不同的粘附素介导。 对链球菌的表达调控知之甚少 粘附素或链球菌粘附素呈递的细胞途径。 我们的实验室最近发现了一种与ATP结合的膜转运 与FIMA关联的系统。我们已经开发出一种有效的方法来 副血链霉菌的定点等位基因置换突变 极大地方便了对该细菌的普通分析。有了这些 工具，我们的实验室在表征领域方面具有独特的地位 FIMA与唾液膜粘连的关系及其特征 它在细胞表面的表达和呈现。具体来说， 我们建议： 1.鉴定FIM基因座上的其他基因及其启动子。 2.研究FIM基因座编码蛋白的表达。 3.鉴定FIMA的活性结合域(S)。 4.通过互补发现额外的黏附相关基因 副角叉链球菌非粘附性突变体的突变。 副血链球菌粘附性的分子和遗传学特征 随着在本发明中开发的工具，现在可以对牙齿表面进行处理 实验室。这项研究将为细菌领域的发展做出贡献。 口腔环境中的粘附性以及对基本的理解 链球菌的遗传学。FIMA样链球菌的作用 作为双功能粘附素的蛋白质参与启动和 牙菌斑的多种多样堆积有待进一步研究。 我们的工作还将探索可能的功能和进化 基材结合与运输的关系，以及胶粘剂 与底物结合。从这样的研究中得到的治疗试剂 因为现在的人可以在控制牙科方面发挥重要作用 斑块的发展和随后的疾病过程。

The overall goal of this proposal to characterize expression of the fimbrial adhesin (FimA) of Streptococcus parasanguis FW213 at the molecular level. This protein, which is highly conserved throughout the sanguis streptococci, has been shown to be an adhesin in members of at least two of the four genetic groups of sanguis a substrate for subsequent accretion of pathogenic species. Data from several laboratories strongly suggest that ecological succession takes place in the formation and development of dental plaque, and that the sanguis (SHA) appears to be mediated by several distinct adhesins. Little is understood of the control of expression of streptococcal adhesins or the cellular pathway of streptococcal adhesin presentation. Our laboratory has recently identified an ATP-binding membrane transport system associated with FimA. We have developed an efficient method for site-specific allelic replacement mutagenesis in S. parasanguis, which greatly facilitates generic analysis of this bacterium. With these tools, our laboratory is uniquely positioned to characterize the domains of FimA involved in adhesion to the salivary pellicle and to characterize its expression and presentation on the surface of the cell. Specifically, we propose: 1. To identify other genes in the fim locus and identify its promoter. 2. To characterize the expression of proteins encoded by the fim locus. 3. To characterize the active binding domain(s) of FimA. 4. To identify additional adhesion-related genes by complementing mutations in nonadherent mutants of S. parasanguls. Molecular and genetic characterization of the adhesion of S. parasanguis to dental surfaces is now possible, with the tools developed in this laboratory. This research will contribute to the field of bacterial adhesion in the oral environment as well as to the basic understanding of the genetics of streptococci. The role of FimA-like streptococcal proteins as bifunctional adhesins involved in both initiation and multigeneric accumulation of dental plaque needs to be further studied. Our work will also explore the possible functional and evolutionary relationship between substrate binding and transport, and adhesive binding to a substrate. Therapeutic reagents resulting from studies such as the present one could have an important role in controlling dental plaque development and the subsequent disease processes.