Polymicrobial Synergy between Treponema denticola and Porphyromonas gingivalis

项目摘要 表现出协同致病性的多微生物群落引起牙周病， 人类的常见传染病。作为研究多微生物协同作用的模型系统，我们正在调查 齿垢密螺旋体和牙龈卟啉单胞菌的相互作用。异型群落的发展是 生理上相容的生物体调节它们自己和它们的伴侣的生理，导致增强的 适合度和毒性。协同代谢可以减少整个群落的营养需求， 从而增加致病潜力。T.齿垢和P. ginigvalis显示代谢交叉喂养， 促进两种细菌的生长。龈下菌斑群落的其他细菌成员是 在代谢交换中协同作用然而，代谢交叉喂养的分子细节以及如何 其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描述 T.牙垢和牙龈卟啉单胞菌，以更好地了解的致病潜力， 社区目标1将评估甘氨酸是如何获得和利用作为碳和能源。目标2将 描述了T.通过增强生物膜的发育， 侵入牙龈上皮细胞。目标3将证明代谢交叉喂养增强了 T.齿垢我们的总体长期目标是将这些新的分子机制转化为 发展针对多种微生物致病菌群的未来治疗方法。的 候选人米勒博士对牙周病的微生物学有着长期的兴趣。完成后 在辅导（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， 他计划继续研究促进牙周病的细菌间相互作用。K99/R00 该提案旨在补充米勒博士以前的研究专长，并为他提供机会 发展必要的技能和经验，成为一个独立的研究科学家。米勒医生会 在主要导师Richard拉蒙博士和共同导师Dr. 大卫斯科特。两位导师都是精心挑选的，因为他们各自贡献了不同但互补的内容。 专业知识，以成功完成这项研究计划。此外，米勒博士还组装了一个 一个由具有各种背景的科学家组成的委员会，他们将提供监督，并为他的科学和职业生涯提供建议。 在向独立过渡的过程中。

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.