Investigation of FadA adhesin from Fusobacterium nucleatum

具核梭杆菌 FadA 粘附素的研究

基本信息

批准号：
10689763
负责人：
Yiping Han
金额：
$ 55.4万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-10 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10689763
关键词：
Alveolar Bone Loss Alzheimer&apos s Disease Amyloid Amyloid Fibrils Amyloid beta-Protein Anaerobic Bacteria Antibodies Bacteria Bacterial Adhesins Binding Biochemical Carcinoma Cell surface Cells Colorectal Cancer Communities Complex Congo Red Data Detergents Disease Dyes E-Cadherin Endothelial Cells Epithelial Cells Exhibits Fusobacterium Fusobacterium nucleatum Genetic Gingiva Growth Human In Vitro Infection Inflammatory Inflammatory Response Invaded Investigation Laboratories Large Intestine Carcinoma Light Malignant neoplasm of gastrointestinal tract Microbial Biofilms Modeling Molecular Mus Non-Insulin-Dependent Diabetes Mellitus Oral Oral cavity Organism Pathogenesis Pathogenicity Peptides Periodontal Diseases Periodontal Infection Periodontal Pocket Periodontitis Phase Placenta Play Pregnancy Complications Prevention Process Production Property Proteins Reaction Recombinants Regulation Research Resistance Resolution Role Series Site Structure Therapeutic Virulence Virulence Factors adverse pregnancy outcome cadherin 5 cancer cell cytokine human disease in vivo interdisciplinary approach medical attention mouth squamous cell carcinoma mutant novel opportunistic pathogen oral bacteria oral cavity epithelium oral commensal pathogen periodontopathogen protein aggregation response scaffold therapeutic target

项目摘要

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.

项目概要具核梭杆菌 (Fn) 是一种革兰氏阴性口腔共生菌，很快引起了人们的关注医疗和研究社区。它是一种机会性病原体，与牙周病以及牙周病有关。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 Fn 的一种新型粘附素和关键毒力因子。 Fn 需要 Fn 才能结合并侵入上皮细胞和内皮细胞并定植于胎盘和结直肠癌。 FadA 与 VE-钙粘蛋白结合上皮细胞和结直肠癌细胞上的内皮细胞和 E-钙粘蛋白，诱导不同的反应不同的宿主细胞。我们最近的研究表明 FadA 的调控和分泌存在差异。所分泌的 FadA 表现出类淀粉样蛋白的特性，并与毒力增加相关。由于 Fn 被认为是主要的共生生物，问题是它如何从共生生物转变为病原体。我们的中央假设是共生状态和致病状态是通过 FadA 的调节来决定的。在在此应用中，我们建议表征 FadA 的淀粉样蛋白样特性，识别涉及的成分其分泌，并确定其在生物膜形成和牙周感染中的作用。这项研究非常意义重大，因为它表征了参与的病原体的一种新颖且关键的毒力成分多种使人类衰弱的疾病。我们的研究结果将确定预防和治疗的治疗目标治疗一系列人类口腔内外疾病。