Molecular Mechanism of F. Nucleatum Virulence

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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.