Microbial methylglyoxal promotes periodontal inflammation

微生物甲基乙二醛促进牙周炎症

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要 Tannerella Forsythia是一种领先的病原体，与牙周炎有关，这是一种常见的慢性病牙齿支持设备（牙周）的炎症通常会导致牙齿成人损失。 T. Forsythia产生高反应性的亲电化合物甲基乙二醇（MGO），可以化学修改和交联生物分子，破坏其结构功能完整性。 MGO导致已知的形成作为高级糖基化最终产物（年龄），可以激活愤怒（受体的受体年龄）受体，触发持续的促炎和促粘性环境驱动组织损伤。 T. Forsythia产生MGO的能力是由于存在与MGO合成有关的酶，甲基甘氨酸合酶（MGSA）。令人惊讶的是，其他两种主要的牙周病原体与牙周炎有关，即卟啉牙牙龈和treponema牙本质，缺乏任何同源物酶。但是，如果确实从微生物中得出MGO，仍然有待确定 T. Forsythia有助于牙周炎症，以及什么是机械基础 MGO引起的牙周炎症。在这项研究中，我们将检验假设 T. forsythia通过促进年龄产生MGO，参与了A的诱导对牙周组织有害的持续炎症反应。我们将测试我们的通过以下特定目的完成假设：1）分子表征 T. Forsythia mgo修饰的宿主和细菌蛋白，2）确定MGO的作用在口腔微生物营养不良和t. forsythia诱导的牙周炎中。该研究将增加我们通过阐明了T. Forsythia的致病机制的理解 MGO是细菌的新型毒成分。总体而言，这些知识可能有助于在设计新的治疗方法方面改善了口腔和系统健康。