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，龋齿 是一种多菌性和生态性疾病，正在继续上升。对空间的详细理解 牙菌斑内变形链球菌与邻近菌株的关系及功能相互作用 社区，以及它们对疾病病因学的影响仍然缺乏，而 龋病是，虽然变形链球菌的水平与总体发病率有很好的相关性，但有 许多情况下，一个人有很大的变形链球菌负担，但没有疾病。 根据初步数据显示，健康受试者牙菌斑的微生物图谱是 与患龋齿的个体显著不同，我们假设细菌种类与 在牙菌斑中与变形链球菌的直接物理相互作用在 调节变形链球菌的生理和致病性。为了验证这一假设，我们将执行三项 相互关联的目标：目标1：制定一种系统的方法来发现和描述 变形链球菌在不同的牙菌斑群落中的身体互动伙伴。将进行三项化验 开发用来确定变形链球菌与之相互作用的牙菌斑种类，并探索 这些相互作用的生物地理学。目的2：分析受试者口腔微生物样本 不同的龋病严重程度和确定物理上相互作用的变形链球菌的配对物种。临床 来自变形链球菌负担较高且患有晚期龋齿或没有疾病的个人的样本将被 通过目标1中开发的技术进行分析，以确定变形链球菌如何与伴侣和他们的 临床牙菌斑内的空间关系在两个临床组之间不同。目标3：调查 物理互动伙伴对变形链球菌生理和致病性的影响。转录体 代谢组学研究将用于监测与特定伙伴物种的互动对 变形链球菌致病相关基因的表达。这项研究将确定生态环境 并将极大地提高对S. 变种人及其邻居的牙菌斑，也将为未来的研究铺平道路 特定的变形链球菌基因与群落致病性有关。

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.