Characterization of Selenomonas sputigena pathogenesis

脓痰硒单胞菌发病机制的表征

基本信息

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
项目类别：
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

项目摘要

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.

项目概要 Selenomonas sputigena 是一种革兰氏阴性、有鞭毛、能活动的牙周细菌，与牙周炎高度相关。牙周炎。脓痰链球菌在牙周炎牙龈部位比在健康牙龈中更为普遍和丰富。硒单胞菌属常规从牙周样本中分离出来，牙龈炎症长期以来一直被人们所关注。与丰度增加有关。人类口腔微生物组的表征强调了这一点许多细菌，包括痰沙门氏菌，都与牙周炎有关。然而，人们对它知之甚少有机体的致病能力。为此，我们最近启动了对 S. 的首次全面研究。痰菌的发病机制和毒力特性。我们证明痰沙门氏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. sputigena 逃避识别鞭毛蛋白的 TLR5 激活。这在临床上很重要，因为我们的初步数据证明运动和趋化基因在牙周炎期间高度表达。此外，S. 痰菌密集地堆积在斑块生物膜内，有助于其结构组织，并与多种微生物群落中的其他牙周细菌。最后，S. sputigena 产生次生信使 c-di-GMP，调节运动和生物膜的形成。我们的科学前提是动力和生物膜的形成是导致牙周病的毒力因素。根据我们的初步数据和文献，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。这项研究的目的将检验我们的假设有两种方法：1）我们将确定生物膜中和浮游生长期间的 c-di-GMP 水平，同时识别结合 c-di-GMP 并执行效应子功能的蛋白质，2) 我们将表征脓毒链球菌在小鼠模型中引起的免疫介质、白细胞浸润和牙槽骨丢失感染。成功完成这项研究将增进我们对长期被认可但知之甚少的一个领域的理解。了解牙周病原体。目前牙周炎的治疗策略是基于很少有明确特征的致病菌。尚未充分研究的细菌（例如痰沙门氏菌）的参与牙周炎的发生和进展，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。