GLUCAN BINDING PROTEINS OF ORAL STREPTOCOCI

变形链球菌是公认的主要病原体。 龋齿。变形链球菌最显著的毒力因素包括 它的耐酸性以及它合成葡聚糖的能力 附着在牙齿表面上。最近的研究表明， 黏附和聚集机制的复杂性。变形链球菌 物种至少有三种葡萄糖转移酶(GTF)，它们是 能够合成各种形式的葡聚糖。此外， 变形链球菌的葡聚糖结合蛋白(GBP)，它似乎是 这一物种，已经被假设为有助于粘附性和 形成粘性斑块。这项建议旨在确定 GBP结合葡聚糖到细胞表面。尤其是， GBP的表达与蔗糖的可利用性有关，而 银杏叶蛋白与细胞表面及不同形态葡聚糖的结合能力 将进行测试，以评估英镑的相对贡献， 葡聚糖聚合物和GTF在粘连和斑块形成中的作用。相遇 这些目标提出了以下具体目标：1)与 GBP表达水平对蔗糖利用率和其他环境的影响 PH值和厌氧菌等参数。2)确定功能 GBP和GTF重复区域的相似性。具体地说，聚变 蛋白质将通过交换重复区域来确定 对葡聚糖结合和GTF酶活性的影响。3)使用 人工合成的寡肽竞争性抑制GBP与其结合 葡聚糖，从而评估不同领域的相对重要性 GBP与葡聚糖结合。4)检验GBP和GTF作为 在细胞上可溶和不溶的葡聚糖黏附之间的桥梁 浮出水面。5)葡聚糖结合凝集素基因的克隆与鉴定 (GBL)。确定的进化关联性 GBL和GBP及其在结构和功能上的相似性 编码的蛋白质产品。这些实验的结果应该会导致 为了更好地理解葡聚糖结合蛋白是如何 变形链球菌促进菌斑形成和龋病 进程。

Streptococcus mutans is recognized as the principal etiologic agent of dental caries. The most prominent virulence factors of S. mutans include its aciduricity, and its ability to synthesize glucans which promote adherence to the tooth surface. Recent studies have demonstrated the complexity of the mechanisms of adhesion and aggregation. S. mutans species have at least three glucosyltransferase (GTF) enzymes which are capable of synthesizing various forms of glucan. Additionally, the glucan-binding protein (GBP) of S. mutans, which appears to be unique to this species, has been hypothesized to contribute to adhesion and the formation of cohesive plaque. This proposal seeks to determine the role of GBP in binding glucans to the cell surface. In particular, the expression of GBP will be related to sucrose availability, and the binding ability of GBP at the cell surface and to various forms of glucan will be tested in order to evaluate the relative contributions of GBP, glucan polymers, and GTFs in adhesion and plaque formation. To meet these objectives the following specific aims are proposed: 1) Relate the level of GBP expression to sucrose availability and other environmental parameters such as pH and anaerobiosis. 2) Determine the functional similarity of the GBP and GTF repeat regions. Specifically, fusion proteins will be created by exchanging the repeat regions to determine the effects on glucan binding and GTF enzymatic activity. 3) Use synthesized oligopeptides to competitively inhibit the binding of GBP to glucans and thereby evaluate the relative importance of different domains of GBP to glucan binding. 4) Test the hypothesis that GBP and GTFs act as bridges between soluble and insoluble glucan adherence on the cell surface. 5) Clone and characterize the gene for the glucan-binding lectin (GBL) of Streptococcus downei. Determine the evolutionary relatedness of gbl and gbp, and the structural and functional similarities of their encoded protein products. The results from these experiments should lead to a better understanding of how the glucan binding proteins of the mutans streptococci contribute to plaque formation and the caries process.