Streptococcus mutans strain susceptibility differences to host defense peptides

描述（由申请人提供）：宿主防御肽在先天免疫中的作用和共生菌群的形成才刚刚开始被定义。变形链球菌是牙菌斑内的一种共生菌，当宿主的饮食选择包括大量的蔗糖时，它可以达到龋齿的比例。然而，变形链球菌的菌株变异在DNA水平上是相当可观的，因此我们有理由期望菌株变异在致龋潜能上也存在，包括抵抗宿主免疫机制的不同能力。本应用旨在验证变形链球菌菌株对宿主防御肽的敏感性模式不同的假设。因此，我们认为这些肽的宿主特异性数量和分布会影响特定变形链球菌菌株的斑块定植，从而有助于确定总体龋齿风险。为了验证这一假设，提出了两个具体目标。目的1将检测从龋齿活跃和无龋齿儿童的牙菌斑样本中分离的变形链球菌克隆，并确定它们对一组口腔宿主防御肽的易感性模式。Aim 2将测量与Aim 1唾液样本相对应的唾液样本中自然存在的宿主防御肽水平，并确定宿主防御肽的分布和数量、独特突变链球菌基因型的易感性谱和儿童龋齿状况之间的相关性水平。这项研究的完成将提供关于宿主先天免疫的潜在贡献的信息，以宿主防御肽的形式，塑造变形链球菌的定植，从而带来龋齿风险。这一信息也将有助于评估宿主防御肽作为治疗性抗龋剂的潜在功效。

DESCRIPTION (provided by applicant): The contributions of host defense peptides in innate immunity and the shaping of the commensal flora are just beginning to be defined. Streptococcus mutans is a commensal within dental plaque that can attain cariogenic proportions when host dietary choices include significant amounts of sucrose. However, S. mutans strain variability is considerable at the DNA level and so it is reasonable to expect that strain variability in cariogenic potential also exists, including differing abilities to resist host immune mechanisms. This application proposes to test the hypothesis that S. mutans strains vary in their susceptibility patterns to host defense peptides. As a consequence we believe that the host-specific quantity and distribution of these peptides influences plaque colonization by particular S. mutans strains thereby helping to define overall caries risk. To test the hypothesis two specific aims are proposed. Aim 1 will examine S. mutans clones isolated from plaque samples obtained from caries-active and caries-free children and determine their susceptibility patterns to a panel of oral host defense peptides. Aim 2 will measure naturally occurring levels of host defense peptides in saliva samples corresponding to the saliva samples from Aim 1, and determine the levels of correlation between the distribution and quantity of host defense peptides, the susceptibility profiles of unique S. mutans genotypes, and the caries status of the children. The completion of this study will provide information regarding the potential contribution of host innate immunity, in the form of host defense peptides, to shape S. mutans colonization and therefore caries risk. This information will also be useful in assessing the potential efficacy of host defense peptides as therapeutic anti-caries agents. PUBLIC HEALTH RELEVANCE: This project will test the hypothesis that different strains Streptococcus mutans, the primary bacterial cause of dental caries, vary in their susceptibilities to host defense peptides. The hypothesis will be tested by assessing the levels of correlation between the distribution and quantity of host defense peptides, the susceptibility profiles of unique S. mutans genotypes, and the caries status of the children. The results will help determine the extent to which host innate immunity may influence colonization of dental plaque with particular strains of S. mutans and may therefore shape overall caries risk.