Pyruvate oxidase: a molecular determinant of commensalism among the oral microbiome

项目摘要 龋病是最常见的口腔疾病之一。尽管有几十年的严重龋齿 研究表明，在疾病预防方面只取得了渐进的进展。龋齿是由 因发酵酸破坏牙齿结构而导致的多菌素代谢失调和无法治愈 与龋齿相关的细菌种类的副产品。因此，应该大力强调 预防龋齿。龋病风险评估(CRA)是一种被广泛接受的龋病评估方法 预防，但一直受到批评，因为它导致患者风险增加而不是 已确认身份。CRA的一个缺点是没有考虑到龋病的多菌性。 此外，它缺乏直接在龋齿牙面取样的分子标记。 发生。改善CRA和预防的关键是更好地理解分子 促进与一般口腔健康相关的口腔共生的机制。我们有 确定了共生口腔链球菌的一个重要特征，它促进了分子 共生性：丙酮酸氧化酶SpxB在有氧条件下提供生长优势 条件，因为它的代谢活动产生额外的三磷酸腺苷以及病原体抑制 过氧化氢。因此，SpxB使早期共生链球菌无法生长并受到抑制 过氧化氢敏感和与龋齿相关的物种。我们的假设是共生性链球菌 产生更多对新陈代谢重要的ATP和抑制过氧化氢 具有竞争性，从而使牙菌斑能够更好地抵抗龋病。我们 因此，提出以下具体目标： 目的1：细胞背景--决定不同过氧化氢产生的分子机制。 目的2：口腔环境-确定spxB调节是否影响体内的竞争力。 目标3：临床背景--过氧化氢产生和spxB表达的实时测量 来自体外牙菌斑。 建议的目标将支持我们更好地了解与健康相关的特征的总体目标 并导致龋病研究的范式向分子研究转变 共生论；口腔微生物学中一个研究极少的领域。获得者 知识将为制定新的预防战略提供重要的新见解。 像龋齿这样的口腔疾病。

Project Summary Caries is one of the most prevalent oral diseases. Despite several decades of substantial caries research, only incremental progress has been made in disease prevention. Caries is the result of polymicrobial dysbiosis and not curable since the tooth structure is destroyed by fermentative acid by-products from caries-associated bacterial species. Therefore, strong emphasis should be on caries prevention. Caries risk assessment (CRA) is a widely accepted approach to caries prevention, but has been criticized because it leads to patients with increased risk not being identified. One drawback of CRA is that the polymicrobial nature of caries is not considered. Furthermore, it lacks any molecular markers sampled directly at the tooth surface where caries occurs. A key to improved CRA and prevention is a better understanding of molecular mechanisms that promote oral commensals associated with general oral health. We have identified an important trait of commensal oral streptococci that promotes molecular commensalism: the pyruvate oxidase, SpxB, provides a growth advantage under aerobic conditions since its metabolic activity generates additional ATP as well as pathogen-inhibiting H2O2. SpxB therefore enables early commensal streptococci to outgrow and inhibit H2O2 susceptible and caries-associated species. Our hypothesis is that commensal streptococci producing higher amounts of metabolically important ATP and inhibitory H2O2 are more competitive and thus allow dental plaque to be more resistant to cariogenic dysbiosis. We therefore propose the following Specific Aims: Aim 1: Cellular context - molecular mechanisms determining differential H2O2 production. Aim 2: Oral context - determine whether spxB regulation influences competitiveness in vivo. Aim 3: Clinical context - Real time measurements of H2O2 production and spxB expression from ex vivo dental plaques. The proposed aims will support our overall goal to better understand the health-associated traits of oral commensals and lead to a paradigm shift in caries research towards that of molecular commensalism; a vastly understudied area of oral microbiology. The gained knowledge will provide important new insight into the development of new strategies to prevent oral diseases like caries.