Investigation of FadA adhesin from Fusobacterium nucleatum

项目摘要 核梭杆菌(Fn)是一种革兰氏阴性杆菌，迅速引起人们的注意。 医学界和研究界。它是一种机会性病原体，与牙周疾病以及 许多口腔外部位的感染，包括不良妊娠结局和结直肠癌。法达是 一种新的粘附素和FN的关键毒力因子。FN需要结合和侵袭上皮细胞，并 内皮细胞，并定植于胎盘和结直肠癌。FADA与VE-钙粘蛋白结合 内皮细胞和E-钙粘附素在上皮细胞和结直肠癌细胞上的表达，诱导不同的反应 不同的宿主细胞。我们最近的研究表明，FADA是有差异的调节和分泌的。隐秘的 FADA表现出淀粉样属性，并与毒力增加相关。由于FN被认为是主要的 对于共生生物体，问题是它如何从共生体转换为病原体。我们的中央 假说认为，共生和致病状态是通过调节FADA来决定的。在……里面 在这一应用中，我们建议表征FADA的淀粉样属性，识别涉及的成分 并确定其在生物膜形成和牙周感染中的作用。这项研究具有很高的 意义重大，因为它表征了一种新的和关键的毒力成分，来自一种涉及 多种使人衰弱的疾病。我们的研究结果将确定预防和治疗的目标 口腔内外一系列人类疾病的治疗。

Project Summary Fusobacterium nucleatum (Fn) is a Gram-negative oral commensal that is quickly attracting attention of the medical and research community. It is an opportunistic pathogen implicated in periodontal disease as well as in infections at numerous extra-oral sites, including adverse pregnancy outcomes and colorectal cancer. FadA is a novel adhesin and key virulence factor from Fn. It is required from Fn to bind and invade epithelial and endothelial cells and to colonize the placenta and colorectal carcinoma. FadA binds to VE-cadherin on endothelial cells and E-cadherin on epithelial and colorectal cancer cells, inducing varying responses from different host cells. Our recent study reveals that FadA is differentially regulated and secreted. The secreted FadA exhibits amyloid-like properties and correlates with increased virulence. As Fn is considered a primarily commensal organism, the question arises how it switches from a commensal to a pathogen. Our central hypothesis is that the commensal and pathogenic states are determined through regulation of FadA. In this application, we propose to characterize the amyloid-like properties of FadA, identify components involved in its secretion, and determine its role in biofilm formation and periodontal infection. This study is highly significant because it characterizes a novel and critical virulence component from a pathogen involved in multiple debilitating human diseases. Results from our study will identify therapeutic targets for prevention and treatment of a series of human diseases within and beyond the oral cavity.