Streptococcus mutans strain susceptibility differences to host defense peptides

描述(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确定。变形链球菌是牙菌斑中的一种共生菌，当宿主的饮食选择包括大量蔗糖时，它可以达到龋齿的比例。然而，变形链球菌在DNA水平上的变异性很大，因此有理由预计菌株的致龋性也存在变异性，包括抵抗宿主免疫机制的不同能力。这项应用提出了一种假设，即变形链球菌菌株对宿主防御肽的敏感性模式不同。因此，我们认为这些多肽的宿主特异性数量和分布影响特定变形链球菌菌株的菌斑定植，从而有助于确定总体龋病风险。为了检验这一假设，本文提出了两个具体目标。目标1将检测从有龋齿和无龋齿儿童的菌斑样本中分离出的变形链球菌克隆，并确定它们对一组口服宿主防御肽的敏感性模式。目的2将测量与AIM 1的唾液样本相对应的唾液样本中自然产生的宿主防御肽水平，并确定宿主防御肽的分布和数量之间的相关性水平，独特的变形链球菌基因型别的易感性，以及儿童的龋齿状况。这项研究的完成将提供关于宿主天然免疫(以宿主防御肽的形式)对变形链球菌定植从而形成龋病风险的潜在贡献的信息。这一信息也将有助于评估宿主防御肽作为治疗性防龋剂的潜在疗效。 公共卫生相关性：这个项目将检验这样一个假设，即不同菌株的变形链球菌对宿主防御肽的敏感性不同。变形链球菌是龋齿的主要细菌原因。这一假说将通过评估宿主防御肽的分布和数量、独特变形链球菌基因型的易感性以及儿童的龋齿状况之间的相关性水平来检验。这一结果将有助于确定宿主的先天免疫在多大程度上可能影响特定变形链球菌对牙菌斑的定植，从而可能形成总体的龋齿风险。

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.