Microbial methylglyoxal promotes periodontal inflammation

项目总结 连翘单胞菌是引起牙周炎的主要病原体，牙周炎是一种常见的慢性牙周炎。 牙齿支持器官(牙周组织)的炎症，通常导致牙齿 成人的损失。连翘产生一种高活性的亲电化合物 甲基乙二醛(MGO)，可以对生物分子进行化学修饰和交联， 破坏了它们的结构和功能的完整性。氧化镁导致了已知的 作为晚期糖基化终产物(AGEs)，可激活RAGE(受体)。 AGEs)受体，触发持久的促炎和促黏附环境 以驱使组织受损。连翘产生MGO的能力是由于其存在 指参与合成氧化镁的一种酶，即甲基乙醛合成酶(MgsA)。 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密螺旋体，缺乏任何与此同源的基因 酵素。然而，微生物来源的氧化镁是否真的来自 连翘致牙周炎的机制是什么？ 氧化镁引起牙周组织炎症。在这项研究中，我们将检验这一假设 连翘通过促进AGEs产生MGO参与了AGEs的诱导。 持续的炎症反应对牙周组织不利。我们将测试我们的 通过完成以下特定目标的假设：1)分子表征 连翘MGO修饰寄主和细菌蛋白及2)确定MGO的作用 口腔微生物失调和连翘所致牙周炎。这项研究将增加 通过阐明T.forsythia致病机理的研究 MGO作为细菌的一种新的毒力成分。总体而言，这些知识可能有助于 在改善口腔和全身健康方面设计新的治疗方法。

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.