Microbial methylglyoxal promotes periodontal inflammation

微生物甲基乙二醛促进牙周炎症

• 批准号: 10574281
• 负责人: Rajendra Prasad Settem
• 金额: $ 16.01万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10574281
• 关键词: Adhesives; Adult; Advanced Glycosylation End Products; Alveolar Bone Loss; Amino Acids; Antimicrobial Effect; Atherosclerosis; Attention; Bacteria; Bacterial Adhesins; Bacterial Proteins; Biochemical; Biological; Chemicals; Chronic; Clinical; Collagen; Complex; Data; Development; Diabetes Mellitus; Disease; Environment; Enzyme-Linked Immunosorbent Assay; Enzymes; Forsythia; Gingiva; Gingival Crevicular Fluid; Health; Host Defense; Human; Individual; Infection; Inflammation; Inflammatory; Inflammatory Response; Investigation; Knowledge; Lesion; Mediating; Mediator of activation protein; Modeling; Modification; Molecular; Mus; NF-kappa B; Nature; Oral; Orthologous Gene; Pathogenesis; Pathogenicity; Periodontal Diseases; Periodontal Pocket; Periodontitis; Periodontium; Porphyromonas gingivalis; Process; Proteins; Pyruvaldehyde; Role; Severities; Severity of illness; Side; Signal Transduction; Source; Structure; Systemic disease; Techniques; Testing; Therapeutic; Tissues; Tooth Diseases; Tooth Loss; Tooth structure; Treponema denticola; Virulence Factors; Virulent; Work; adduct; antimicrobial peptide; base; chronic inflammatory disease; crosslink; cytokine; data submission; defined contribution; design; dysbiosis; healing; improved; in vivo; insight; microbial; microbial community; monocyte; mouse model; novel; novel therapeutic intervention; oral bacteria; oral infection; oral microbiome; oral pathogen; pathogen; periodontopathogen; receptor; receptor for advanced glycation endproducts; systemic inflammatory response; tissue repair

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.

项目概要 连翘坦纳菌 (Tannerella forsythia) 是与牙周炎有关的主要病原体，牙周炎是一种常见的慢性牙周炎。 牙齿支撑装置（牙周组织）发炎，通常会导致牙齿脱落 成人的损失。连翘产生高反应性亲电化合物 甲基乙二醛（MGO），可以化学修饰和交联生物分子， 破坏其结构功能完整性。 MGO 导致已知物质的形成 作为晚期糖基化终末产物 (AGE)，它可以激活 RAGE（RAGE 受体） AGEs）受体，触发持久的促炎和促粘附环境 驱动组织损伤。连翘产生 MGO 的能力是由于存在 甲基乙二醛合酶 (MgsA) 参与 MGO 的合成。 引人注目的是，另外两种与牙周炎有关的主要牙周病原体， 即牙龈卟啉单胞菌和齿垢密螺旋体，缺乏任何同源物 酶。然而，仍有待确定，MGO 是否确实是从微生物中衍生而来的。 连翘会导致牙周炎症，其机制基础是什么 MGO 诱发的牙周炎症。在本研究中，我们将检验假设 连翘通过促进 AGEs 产生 MGO 参与诱导 持续的炎症反应对牙周组织有害。我们将测试我们的 通过完成以下具体目标来提出假设：1）分子表征 连翘 MGO 修饰宿主和细菌蛋白以及 2) 确定 MGO 的作用 口腔微生物失调和连翘引起的牙周炎。研究会增加 通过阐明连翘的作用，我们对连翘的致病机制有了了解 MGO 作为细菌的一种新型有毒成分。总的来说，这些知识可能会有所帮助 设计改善口腔和全身健康的新治疗方法。