Characterization of Selenomonas sputigena pathogenesis

脓痰硒单胞菌发病机制的表征

• 批准号: 10810907
• 负责人: Daniel Patrick Miller
• 金额: $ 30.14万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-11 至 2025-09-10
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10810907
• 关键词: 16S ribosomal RNA sequencing; Alveolar Bone Loss; Bacteria; Binding; Binding Proteins; Biological Response Modifiers; Bone Resorption; Characteristics; Chemotaxis; Clinical; Communities; Community Developments; Data; Development; Disease; Disease Progression; Epithelial Cells; Experimental Models; Flagellin; Funding; Future; Genes; Gingiva; Goals; Growth; Health; Human; In Vitro; Infection; Inflammation; Inflammation Mediators; Inflammatory; Innate Immune Response; Knowledge; Leucocytic infiltrate; Life Style; Literature; Mastigophora; Mediating; Metabolism; Microbial Biofilms; Modeling; Motor; Mus; Oral Characters; Organism; Osteitis; Outcome; Pathogenesis; Pathogenicity; Patients; Periodontal Diseases; Periodontitis; Physiological; Physiology; Property; Proteins; Publications; Regulation; Role; Sampling; Selenomonas; Selenomonas sputigena; Signal Transduction; Site; Structure; System; TLR5 gene; Testing; Therapeutic; Virulence; Virulence Factors; alveolar bone; bone loss; cell motility; cytokine; dental biofilm; dysbiosis; fitness; human disease; in vivo; microbial; mouse model; novel strategies; novel therapeutics; oral microbiome; pathobiont; pathogenic bacteria; periodontopathogen; polymicrobial biofilm; prevent; recruit; response; sensor; tissue culture

Project Summary Selenomonas sputigena is a Gram-negative, flagellated, motile periodontal bacteria highly associated with periodontitis. S. sputigena is more prevalent and abundant in periodontitis gingival sites than in healthy gingiva. Selenomonas spp. are routinely isolated from periodontal samples, and gingival inflammation has long been associated with an increased abundance. Characterization of the human oral microbiome has highlighted that many bacteria, including S. sputigena, are associated with periodontitis. However, very little is known about the pathogenic capabilities of the organism. To that end, we recently initiated the first comprehensive study of S. sputigena pathogenesis and virulence properties. We demonstrated S. sputigena binds to gingival epithelial cells and promotes extensive pro-inflammatory cytokine secretion. Interestingly, we observed that S. sputigena evaded TLR5 activation, which recognizes flagellin. This is clinically important as our preliminary data demonstrate that motility and chemotaxis genes are highly expressed during periodontitis. Additionally, S. sputigena is densely packed within plaque biofilm, contributing to its structural organization, and interacts with other periodontal bacteria in polymicrobial communities. Finally, S. sputigena produces the secondary messenger c-di-GMP, which regulates motility and biofilm development. Our scientific premise is that motility and biofilm development are virulence factors that contribute to periodontal disease. Based on our preliminary data and the literature, we hypothesize that S. sputigena c-di-GMP regulates lifestyle decisions between motility and biofilm formation, impacting inflammation and pathogenicity. The aims of this study will test our hypothesis in two approaches: 1) we will determine c-di-GMP levels in biofilms, and during planktonic growth, while identifying the proteins that bind c-di-GMP and carry out effector functions and, 2) we will characterize the immune mediators, leukocyte infiltration and alveolar bone loss caused by S. sputigena in murine models of infection. Successful completion of this study will advance our understanding of a long-recognized but poorly understood periodontal pathogen. Current therapeutic strategies for periodontitis were developed based on a few well-characterized pathogenic bacteria. The involvement of under-studied bacteria, such as S. sputigena, in the initiation and progression of periodontitis, may lead to re-evaluating treatment approaches or uncovering novel strategies to prevent or treat periodontitis.

项目摘要 生痰月形单胞菌是一种革兰氏阴性、有鞭毛、能动的牙周细菌， 牙周炎S.痰菌在牙周炎牙龈部位比在健康牙龈中更普遍和丰富。 月形单胞菌属通常从牙周样本中分离出来，牙龈炎症长期以来一直是 与丰富度的增加有关。人类口腔微生物组的表征强调， 许多细菌，包括S. sputigena与牙周炎有关。然而，人们对它知之甚少。 生物体的致病能力。为此，我们最近发起了第一个全面的研究S。 痰菌的发病机制和毒力特性。我们证明了S。痰菌与牙龈上皮细胞结合 并促进广泛的促炎细胞因子分泌。有趣的是，我们观察到S。吐痰 逃避识别鞭毛蛋白的TLR 5激活。这在临床上很重要，因为我们的初步数据 表明牙周炎期间运动和趋化基因高度表达。此外，S. 产痰菌在菌斑生物膜内密集堆积，有助于其结构组织，并与 其他牙周细菌在多微生物群落。最后，S。sputigena产生次级 信使c-di-GMP，其调节运动性和生物膜发育。我们的科学前提是 和生物膜形成是导致牙周病的毒力因子。根据我们初步的 数据和文献，我们假设S。sputigena c-di-GMP调节运动之间的生活方式决定 和生物膜形成，影响炎症和致病性。本研究的目的是验证我们的假设 在两种方法中：1）我们将确定生物膜中和在非稳态生长期间的c-di-GMP水平， 鉴定结合c-di-GMP并执行效应器功能的蛋白质，2）我们将表征 免疫介质、白细胞浸润和牙槽骨丢失。sputigena在小鼠模型 感染这项研究的成功完成将促进我们对一个长期公认的，但很少 了解牙周病原体。目前牙周炎的治疗策略是基于 很少有特征明确的致病菌。研究不足的细菌，如S。痰，因 牙周炎的发生和发展，可能会导致重新评估治疗方法或发现 预防或治疗牙周炎的新策略。