Microbial methylglyoxal promotes periodontal inflammation

项目摘要 坦纳氏菌是与牙周炎有关的主要病原体，牙周炎是常见的慢性牙周炎。 牙齿支持装置（牙周组织）的炎症，经常导致牙齿 成年人的损失。T.西印度群岛会产生一种活性很高的亲电化合物 甲基乙二醛（MGO），它可以化学修饰和交联生物分子， 破坏了它们的结构功能完整性MGO导致了已知的 作为晚期糖基化终产物（AGEs），其可以激活β-淀粉样蛋白受体（β-淀粉样蛋白受体，β-淀粉样蛋白受体）， AGEs）受体，触发一个永久的促炎和促粘附环境 造成组织损伤T.阿斯塔纳生产MGO是由于存在 一种酶，甲基乙二醛合成酶（MgsA），参与MGO的合成。 引人注目的是，与牙周炎有关的另外两种主要牙周病原体， 即牙龈卟啉单胞菌和齿垢密螺旋体缺乏任何同源物 酵素然而，还有待确定的是，是否真的是微生物来源的MGO， T.牙周炎的发病机制是什么？ MGO诱导的牙周炎。在这项研究中，我们将测试假设 这个T。通过促进AGEs产生的MGO参与诱导一种 对牙周组织有害的持续炎症反应。我们将测试我们的 通过完成以下具体目标的假设：1）分子表征 T. MGO修饰的宿主和细菌蛋白，以及2）确定MGO的作用 在口腔微生物生态失调和T.牙周炎的病因研究将增加 我们对T.通过阐明 MGO作为一种新的有毒成分的细菌。总的来说，这些知识可能有助于 设计新的治疗方法，改善口腔和全身健康。

Project summary Tannerella forsythia is a leading pathogen implicated in periodontitis, a common chronic inflammation of the tooth-supporting apparatus (periodontium) that often results in tooth loss in adults. T. forsythia produces a highly reactive electrophilic compound methylglyoxal (MGO), which can chemically modify and cross-link biomolecules, disrupting their structure-function integrity. MGO causes the formation of what are known as the advanced glycation endproducts (AGEs), which can activate RAGE (receptor of AGEs) receptor, trigger a perpetuating pro-inflammatory, and pro-adhesive environment to drive tissue damage. The ability of T. forsythia to produce MGO is due to the presence of an enzyme, methylglyoxal synthase (MgsA), involved in the synthesis of MGO. Strikingly, the other two dominant periodontal pathogens implicated in periodontitis, namely Porphyromonas gingivalis and Treponema denticola, lack any homologs of this enzyme. It remains to be determined, however, if indeed microbially derived MGO from T. forsythia contributes to periodontal inflammation and what is the mechanistic basis of MGO-induced inflammation in the periodontium. In this study we will test the hypothesis that T. forsythia produced MGO by promoting AGEs is involved in the induction of a sustained inflammatory response detrimental to the periodontal tissues. We will test our hypothesis by completion of the following specific aims: 1) Molecular characterization of T. forsythia MGO modified host and bacterial proteins and 2) Determine the role of MGO in oral microbial dysbiosis and T. forsythia induced periodontitis. The study will increase our understanding of the pathogenic mechanisms of T. forsythia by elucidating the role of MGO as a novel virulent component of the bacterium. Overall, this knowledge might aid in designing new therapeutic approaches in improving oral and systemic health.