Understanding S. mutans pathogenesis in a social and ecological setting

项目摘要 虽然变形链球菌经常被认为是龋齿的主要病原体，但有证据表明， 是一种多微生物和生态疾病继续上升。详细了解空间 S.牙菌斑内的变形菌及其邻居 社区，以及它们对疾病病因学的影响仍然缺乏，其中一个未解之谜， 龋病学的一个重要特征是，S.变形杆菌与疾病发病率总体相关， 许多情况下，其中一个人有一个重大的负担S。变异，但没有疾病。 基于表明健康受试者牙菌斑的微生物概况的初步数据， 与患龋的个体显著不同，我们假设， 与S的直接物理相互作用。牙菌斑联合体中的变异体在 调节S.变种人为了验证这一假设，我们将进行三个 目标1：制定一种系统的方法， 与S.在不同的牙菌斑社区中的变形菌。将进行三次测定， 开发用于确定S.变异人的身体相互作用和探索 这些互动的流程图。目的2：分析来自人类受试者的口腔微生物样品， 不同的龋齿严重程度，并确定物理相互作用的合作伙伴物种的S。变异人临床 样本来自S值高的个体。无论是晚期龋齿还是无疾病， 通过目标1中开发的技术进行分析，以确定S.变异体相互作用的伙伴和他们的 两个临床组之间的临床牙菌斑内的空间关系不同。目标3：调查 身体上相互作用的伴侣对S.变形菌生理学和致病性。转录组 代谢组学研究将用于监测与特定伴侣物种的相互作用对 参与S.变种人这项研究将确定生态 指纹图谱的研究，将大大增加对S. mutans及其邻居在牙菌斑社区，也将铺平道路，为未来的研究， 特异性S.变异基因参与社区致病性。

Project Summary While Streptococcus mutans is often cited as the primary etiologic agent of dental caries, evidence that caries is a polymicrobial and ecological disease continues to mount. A detailed understanding of the spatial relationship and functional interaction between S. mutans and its neighbors within the dental plaque community, as well as their impact on disease etiology is still lacking, and one of the unsolved mysteries in cariology is that, while the levels of S. mutans correlate well with the disease incidences overall, there are numerous cases in which an individual has a significant burden of S. mutans, but an absence of disease. Based upon preliminary data indicating that the microbial profile of the dental plaque of healthy subjects was significantly different from that of individuals with caries, we hypothesize that the bacterial species with direct physical interaction with S. mutans within the dental plaque consortium play a critical role in modulating the physiology and pathogenicity of S. mutans. To test this hypothesis, we will carry out three interconnected aims: Aim 1: Developing a systematic approach to discover and characterize the physically interacting partners of S. mutans in a diverse dental plaque community. Three assays will be developed to determine the dental plaque species with which S. mutans physically interacts and explore the biogeography of these interactions. Aim 2: Analyzing oral microbial samples from human subjects with different caries severity and identifying the physically interacting partner species of S. mutans. Clinical samples from individuals with a high S. mutans burden and either advanced dental caries or no disease will be analyzed by the techniques developed in Aim 1, to identify how the S. mutans interacting partners and their spatial relationship within clinical dental plaque differs between the two clinical groups. Aim 3: Investigating the impact of physically interacting partners on S. mutans physiology and pathogenicity. Transcriptomic and metabolomic studies will be used to monitor the impact of interactions with specific partner species on expression of genes involved in the pathogenesis of S. mutans. This study will identify the ecological fingerprints of cariogenic plaque and will greatly increase the understanding of the relationship between S. mutans and its neighbors in the dental plaque community and will also pave the way for the future study of specific S. mutans genes involved in community pathogenicity.