Polymicrobial Synergy between Treponema denticola and Porphyromonas gingivalis

齿垢密螺旋体和牙龈卟啉单胞菌之间的多种微生物协同作用

基本信息

批准号：
10037674
负责人：
Daniel Patrick Miller
金额：
$ 24.9万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10037674
关键词：
Adherence Alveolar Bone Loss Bacteria Biological Models Carbon Catabolism Cell model Cells Chemotaxis Communication Communities Community Developments Complement Complex Development Disease Disease model Energy-Generating Resources Environment Epithelial Cells Exhibits Future Gingiva Glycine Goals Growth Human Immune response Infection Inflammatory Investigation Link Mediating Mentors Metabolic Metabolism Microbial Biofilms Microbiology Modeling Molecular Movement Mus Nutritional Requirements Organism Outcome Pathogenicity Periodontal Diseases Periodontitis Phase Phenotype Physiological Physiological Processes Physiology Porphyromonas gingivalis Research Rodent Model Role Scientist Signal Transduction Signal Transduction Pathway Source Symbiosis System Therapeutic Training Translating Treponema denticola Universities Virulence bone loss career development cell motility design dysbiosis experience feeding fitness improved in vivo insight interest member microbial community novel novel strategies novel therapeutics periodontopathogen polymicrobial disease prevent professor programs response skills synergism uptake

项目摘要

Project Summary Polymicrobial communities that exhibit synergistic pathogenicity cause periodontal disease, one of the most common infections of humans. As a model system for the study of polymicrobial synergy, we are investigating the interactions of Treponema denticola and Porphyromonas gingivalis. Heterotypic communities develop as physiologically compatible organisms modulate their own and their partner’s physiology resulting in enhanced fitness and virulence. Synergistic metabolism can reduce the nutrient requirements of the entire community, thereby increasing the pathogenic potential. T. denticola and P. ginigvalis display metabolic cross-feeding to enhance the growth of both bacteria. Additional bacterial members of the subgingival plaque community are known to cooperate in metabolic exchanges. However, the molecular details of metabolic cross-feeding and how it functions to drive pathogenicity are understudied. The overall premise of this study is to characterize the metabolic interactions between T. denticola and P. gingivalis to better understand the pathogenic potential of the community. Aim 1 will evaluate how glycine is acquired and utilized as a carbon and energy source. Aim 2 will characterize the response of T. denticola to mutualistic metabolism by enhancing biofilm development and invasion into gingival epithelial cells. Aim 3 will demonstrate that metabolic cross-feeding enhances the pathogenicity of T. denticola. Our overall long-term goal is to translate these novel molecular mechanisms into the development of future therapeutic approaches targeting polymicrobial pathogenic communities. The candidate, Dr. Miller, has a longstanding interest in the microbiology of periodontal diseases. After completing the mentored (K99) phase, his goal is to become an assistant professor at a leading research university, where he plans to continue his research on interbacterial interactions that promote periodontal diseases. This K99/R00 proposal is designed to complement Dr. Miller’s previous research expertise and provide him with the opportunity to develop the necessary skills and experiences to become an independent research scientist. Dr. Miller will receive additional training under the guidance of the primary mentor, Dr. Richard Lamont, and co-mentor, Dr. David Scott. Both mentors were carefully selected for as they each contribute diverse, yet complementary expertise for the successful completion of this research program. Additionally, Dr. Miller has assembled a committee of scientists with various backgrounds who will provide oversight and advise his scientific and career development during his transition to independence.

项目概要表现出协同致病性的多种微生物群落导致牙周病，这是最常见的疾病之一作为研究多种微生物协同作用的模型系统，我们正在研究人类常见感染。齿垢密螺旋体和牙龈卟啉单胞菌的相互作用发展为异型群落。生理上相容的生物体调节自己及其伴侣的生理机能，从而增强适应性和毒力的协同代谢可以减少整个群落的营养需求，从而增加 T. denticola 和 P. ginigvalis 的致病潜力。促进龈下菌斑群落的其他细菌成员的生长。已知在代谢交换中合作，但是，代谢交叉喂养的分子细节以及如何合作。它驱动致病性的功能尚未得到充分研究，本研究的总体前提是表征。 T. denticola 和 P. gingivalis 之间的代谢相互作用，以更好地了解 T. denticola 和 P. gingivalis 的致病潜力目标 1 将评估如何获取甘氨酸并将其用作碳和能源。通过增强生物膜发育和表征 T. denticola 对互利代谢的反应目标 3 将证明代谢交叉喂养增强了牙龈上皮细胞。我们的总体长期目标是将这些新的分子机制转化为 T. denticola 的致病性。针对多种微生物致病菌群的未来治疗方法的开发。候选人米勒博士在完成学业后对牙周疾病微生物学有着长期的兴趣。在指导（K99）阶段，他的目标是成为一所领先的研究型大学的助理教授，在那里他计划继续研究促进牙周病的细菌间相互作用。该提案旨在补充米勒博士之前的研究专业知识，并为他提供机会培养成为一名独立研究科学家所需的技能和经验。在主要导师 Richard Lamont 博士和共同导师 Dr. Richard Lamont 的指导下接受额外培训大卫·斯科特（David Scott）两位导师都是经过精心挑选的，因为他们各自做出了不同的贡献，但又互补。此外，米勒博士还收集了成功完成该研究计划的专业知识。由具有不同背景的科学家组成的委员会，将为他的科学和职业生涯提供监督和建议向独立过渡期间的发展。