MOLECULAR BASIS OF PILUS-MEDIATED GONOCOCCAL ADHESION

菌毛介导的淋球菌粘附的分子基础

• 批准号: 10363679
• 负责人: Alexey Jarrell Merz
• 金额: $ 19.44万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-03 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10363679
• 关键词: Adherence; Adhesions; Adhesives; Affinity; Animal Model; Antibiotics; Bacteria; Bacterial Adhesins; Bacterial Meningitis; Binding; Biochemical; Biogenesis; Bioinformatics; C-terminal; Cells; Data; Development; Docking; Drug resistance; Epithelial; Epithelial Cells; Epitopes; Fiber; Genetic; Goals; Gonorrhea; Human; In Vitro; Infection; Legionella pneumophila; Length; Mediating; Modeling; Molecular; Mucous Membrane; N-terminal; Neisseria; Neisseria gonorrhoeae; Neisseria meningitidis; Pilum; Prevalence; Process; Proteins; Pseudomonas aeruginosa; Public Health; Publishing; Reagent; Recombinants; Signal Transduction; Specificity; Structure; Testing; Therapeutic; Time; Tissues; Tropism; Vaccines; Virulence; Virulence Factors; Work; base; experimental study; genetic testing; improved; in vivo; neutralizing antibody; pathogen; receptor; response

PROJECT SUMMARY Neisseria gonorrhoeae (GC) is a growing public health problem which is likely to worsen due to increasing antibiotic resitance and the lack of a vaccine. Type IV pili (Tfp) are known to be essential for GC virulence in humans, and there is strong evidence that Tfp bind to high-affinity receptors on human cells. However, the identities of both the specific GC protein(s) and host receptor(s) responsible for high-affinity adherence are not known. Twenty years of pubished experiments strongly support the hypothesis that the low-abundance protein PilC is the high-affinity adhesin presented by GC Tfp. However, little is known about the overall structure of PilC, the mechanisms through which it associates with Tfp, and the host receptors that it presumably engages. In this project we will use in vivo genetic tests and in vitro biochemical analyses to test models of PilC functional organization, and we will use the resulting information and reagents to begin the process of identifying high-affinity receptors on human mucosal epithelial cells. The impacts of this project will include clarifying the mechanisms of PilC association with pili, the mechanisms through which PilC influences pilus biogenesis, and the mechanisms through which GC and the closely related pathogen N. meningitidis adhere to human epithelial tissues to initiate infection.

项目摘要 Neisseria Gonorrhoeae（GC）是一个日益增长的公共卫生问题，可能会因增加而恶化 抗生素沉积和缺乏疫苗。已知IV型Pili（TFP）对于GC毒力至关重要 人类，有强有力的证据表明TFP与人类细胞上的高亲和力受体结合。但是， 负责高亲和力依从性的特定GC蛋白和宿主受体的身份不是 已知。二十年的出版实验强烈支持低丰度蛋白的假设 PILC是GC TFP提出的高亲和力粘合剂。但是，关于总体结构知之甚少 PILC，它与TFP相关的机制及其可能参与的宿主受体。 在这个项目中，我们将使用体内基因检测和体外生化分析来测试PILC的模型 功能组织，我们将使用结果信息和试剂开始 鉴定人粘膜上皮细胞上的高亲和力受体。该项目的影响将包括 阐明PILC与Pili的机制，PILC影响pilus的机制 生物发生，以及GC和密切相关的病原体N.脑膜炎粘附到的机制 人上皮组织引发感染。