Molecular Mechanism of F. Nucleatum Virulence

描述：核梭杆菌是一种革兰氏阴性的厌氧细菌，普遍存在于口腔中，通常与牙周病（PD）有关。它也见于身体其他部位的感染和脓肿。特别是，它与早产（PTB）有关。PD最近被认为是肺结核的潜在危险因素。然而，这种相关性背后的机制尚未被阐明。由于其与PD和PTB的相关性，核胞梭菌是研究口腔健康与PTB关系的一个很好的候选者。本研究的重点是在体外研究具核梭菌与宿主细胞的相互作用，为进一步分析具核梭菌在肺结核中的致病作用做铺垫。一种新的黏附素FadA（梭杆菌黏附素A）已被发现与宿主细胞结合。此外，它似乎参与了不同细菌之间的共聚集，这是牙菌斑形成的一个关键特征。我们的假设是FadA是具核梭菌粘附和侵入宿主组织细胞并诱导宿主先天免疫反应的重要毒力因子。本研究的具体目的是：1)研究具核梭菌FadA黏附素在组织细胞附着和侵袭中的作用。2)鉴定FadA的宿主受体，并表征其在核梭菌与宿主细胞相互作用中的作用。本研究的创新之处在于对具核梭菌毒力的分子机制进行了研究。我们的长期目标是了解核梭菌在PD和PTB中的作用，并确定口腔健康与孕产妇健康之间的关系。从这项研究中获得的知识可能有助于未来治疗药物的开发，以减少PD， PTB和其他常见全身感染的发病率。

DESCRIPTION: Fusobacterium nucleatum is a Gram negative, anaerobic bacterium ubiquitous to the oral cavity and often associated with periodontal disease (PD). It is also found in infections and abscesses of other parts of the body. In particular, it is implicated in Preterm birth (PTB). PD is newly recognized as a potential risk factor for PTB. Nevertheless, the mechanism underlying the correlation has not been elucidated. As a result of its association with PD and PTB, F. nucleatum is an excellent candidate to investigate the relationship between oral health and PTB. The focus of this study is to investigate F. nucleatum interactions with host cells in vitro, as a prelude to future analyses of the pathogenic role of F. nucleatum in PTB. A novel adhesin, FadA (Fusobacterium adhesin A), has been identified that binds to host cells. In addition, it appears to be involved in the coaggregation between different bacteria, a key characteristic in Dental plaque formation. Our hypothesis is that FadA is an important virulence factor for F. nucleatum to adhere to and invade host tissue cells and to induce host innate immune responses. The Specific Aims are: 1) To characterize the FadA adhesin from F. nucleatum for its role in tissue cell attachment and invasion. 2) To identify the host receptor for FadA and to characterize its role in F. nucleatum-host cell interactions. The innovative aspect of this study is investigation of the molecular mechanism of the virulence of F. nucleatum. Our long-term goal is to understand the role of F. nucleatum in PD and PTB, and to identify the relationship between oral health and maternal health. Knowledge obtained from this study may enable future development of therapeutic agents to reduce the incidence of PD, PTB, and possibly other common systemic infections.