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和肠道植物群形成中的作用刚刚开始被确定。变形链球菌是牙菌斑内的一种细菌，当宿主的饮食选择包括大量的蔗糖时，变形链球菌可以达到致龋的比例。然而，S.变异株的变异性在DNA水平上是相当大的，因此可以合理地预期，在致龋潜力方面也存在变异性，包括抵抗宿主免疫机制的不同能力。本申请提出检验S.变异株对宿主防御肽的敏感性模式不同。因此，我们认为这些肽的宿主特异性数量和分布影响特定S.变异菌株，从而帮助确定整体龋齿风险。为了检验这一假设，提出了两个具体的目标。目标1将检查S。从龋活跃和无龋儿童的牙菌斑样品中分离的变异株克隆，并确定它们对一组口腔宿主防御肽的易感性模式。目的2将测量与目的1的唾液样品相对应的唾液样品中宿主防御肽的天然存在水平，并确定宿主防御肽的分布和数量之间的相关性水平，独特的S.变形杆菌基因型和儿童的龋齿状况。这项研究的完成将提供有关宿主先天免疫的潜在贡献的信息，以宿主防御肽的形式，形成S。变形菌的定植和由此引起的龋齿风险。这些信息也将有助于评估宿主防御肽作为治疗性抗龋齿剂的潜在功效。 公共卫生相关性：本项目将测试不同菌株变形链球菌（龋齿的主要细菌原因）对宿主防御肽的敏感性不同的假设。通过评估宿主防御肽的分布和数量之间的相关性水平，独特的S.变形杆菌基因型和儿童的龋齿状况。这些结果将有助于确定宿主先天免疫在多大程度上影响特定菌株的牙菌斑定植。变形菌，因此可能形成整体龋齿风险。

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.