Polymicrobial Synergy between Treponema denticola and Porphyromonas gingivalis

项目摘要 表现出协同致病作用的多菌群落会导致牙周病，牙周病是最常见的 人类的常见感染。作为研究多菌种协同作用的模型系统，我们正在研究 齿密螺旋体与牙龈卟啉单胞菌的相互作用异型群落发展为 生理上相容的有机体调节自己和伴侣的生理，从而增强 健康和致命性。协同新陈代谢可以减少整个群落的营养需求， 从而增加致病潜能。齿圆线虫和牙根假单胞菌表现出代谢交叉摄食 促进这两种细菌的生长。龈下菌斑群落的其他细菌成员是 以在新陈代谢交换中合作而闻名。然而，代谢交叉喂养的分子细节以及如何 它在驱动致病性方面的作用还没有被充分研究。这项研究的总体前提是将 齿状念珠菌与牙龈假单胞菌之间的代谢相互作用 社区。目标1将评估甘氨酸是如何获得并作为碳和能源利用的。目标2将 通过促进生物膜的发育和生物膜的形成来表征齿纹夜蛾对互惠代谢的反应 侵入牙龈上皮细胞。目标3将证明代谢交叉喂养增强了 齿纹夜蛾的致病力。我们的总体长期目标是将这些新的分子机制转化为 未来针对多微生物致病菌群的治疗方法的发展。这个 候选人米勒博士对牙周疾病的微生物学有着长期的兴趣。完成后 在指导阶段(K99)，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疾病的细菌间相互作用。这是K99/R00 该提案旨在补充米勒博士之前的研究专长，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。米勒医生会 在主要导师理查德·拉蒙特博士和共同导师理查德·拉蒙特博士的指导下接受额外的培训。 大卫·斯科特。这两位导师都是经过精心挑选的，因为他们的贡献各不相同，但又具有互补性 成功完成这项研究计划的专业知识。此外，米勒博士还组装了一个 由具有不同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事业提供建议 他在向独立过渡的过程中取得了很大进展。

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.