Metabolic modulation of Fusobacterium nucleatum virulence

项目总结 核梭杆菌，一种在口腔生物膜形成中起关键作用的革兰氏阴性厌氧菌， 或牙菌斑，具有逃避宿主免疫并传播到口外部位的非凡能力，包括 胎盘和结肠，在那里它与早产和结直肠癌等重大疾病有关。 到目前为止，我们对核假单胞菌的致病和致病机制还知之甚少。 口外部位的环境因素可能影响这种病原体的毒力潜力。 考虑到乙醇胺(EA)--碳/氮和能源的重要来源，以及一种信号 一些细菌病原体的分子-在胎儿发育过程中胎盘中含量丰富，我们的目标是检测 通过一种特殊的细胞器，细菌微室(BMC)来调节EA代谢的中心假说， 调节核盘藻的毒力潜势。这一假设是基于我们令人信服的初步数据 表明环境电针刺激BMC的形成和电针利用基因的表达，并且 EA分解代谢受阻改变了核盘藻的致病力。此应用程序的主要目标是 研究BMC介导的EA的利用如何影响融合细菌的毒力(目标1)以及EA中的阻断如何 分解代谢调节梭菌致病性(目标2)。我们的研究产生的结果不仅将 提供有关核镰刀菌病理生理学的重要知识和有前景的治疗靶点， 而且有可能推进宿主-病原体相互作用的广泛领域。

PROJECT SUMMARY Fusobacterium nucleatum, a Gram-negative anaerobe that plays a key role in the development of oral biofilms, or dental plaque, has the remarkable ability to escape host immunity and spread to extraoral sites, including placenta and colon, where it is associated with significant diseases such as preterm birth and colorectal cancer. To date, we have a poor understanding of the mechanisms of virulence and disease by F. nucleatum, and the environmental factors in the extraoral sites that potentially affect the virulence potential of this pathogen. Considering that ethanolamine (EA) – an important source of carbon/nitrogen and energy, and a signaling molecule for some bacterial pathogens – is abundant in placenta during fetal development, we aim to test the central hypothesis that regulated EA metabolism via a specialized organelle, bacterial microcompartment (BMC), modulates the virulence potential of F. nucleatum. This hypothesis is based on our compelling preliminary data showing that environmental EA stimulates BMC formation and expression of EA utilization genes, and that blockage in EA catabolism alters the pathogenicity of F. nucleatum. The major goal of this application is to examine how BMC-mediated EA utilization affects fusobacterial virulence (Aim 1) and how blockage in EA catabolism modulates fusobacterial pathogenicity (Aim 2). The results generated from our studies will not only provide important knowledge regarding the pathophysiology of F. nucleatum and promising therapeutic targets, but also have potential to advance the broad field of host-pathogen interactions.