Understanding S. Mutans Pathogenesis in a Social and Ecological Setting

了解社会和生态环境中变形链球菌的发病机制

• 批准号: 9617563
• 负责人: Jonathon Baker
• 金额: $ 2.31万
• 依托单位: J. CRAIG VENTER INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9617563
• 关键词: Understanding; S.; Mutans; Pathogenesis; Social

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.

项目摘要 虽然链球菌突变体经常被认为是龋齿的主要病因学药，但证据表明龋齿 是一种多数菌和生态疾病，继续延伸。对空间的详细理解 S. mutans及其邻居之间的关系和功能相互作用 社区以及它们对疾病病因的影响仍然缺乏 cariology是，虽然链球菌的水平与总体上的疾病发病率很好地相关 许多人承担着巨大的叛变负担，但没有疾病。 基于初步数据，表明健康受试者的牙菌斑的微生物特征是 我们与龋齿的人有明显不同的不同，我们假设 在牙菌菌财团内与S. Mutans的直接物理互动在 调节链球菌的生理和致病性。为了检验这一假设，我们将执行三个 相互联系的目的：目标1：开发一种系统的方法来发现和表征 在多样化的牙菌斑社区中进行身体互动的伴侣。三个测定将是 开发的目的是确定S. mutans进行物理相互作用并探索的牙齿物种 这些相互作用的生物地理学。目标2：分析来自人类受试者的口服微生物样本 不同的龋齿严重程度，并识别出突变链球菌的物理相互作用的伴侣物种。临床 来自较高的S. mutans负担和晚期龋齿或无疾病的人的样本将是 由AIM 1中开发的技术分析，以确定S. Mutans如何相互作用的伙伴及其如何 两个临床组之间的临床牙菌斑内空间关系不同。目标3：调查 物理相互作用的伴侣对链球菌生理和致病性的影响。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 与链球菌发病机理有关的基因的表达。这项研究将确定生态 致癌斑块的指纹，并将大大增加对S之间的关系的理解。 Mutans及其牙科斑块社区中的邻居，也将为未来的研究铺平道路 参与社区致病性的特异性链球菌基因。