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.

项目概要 淋病奈瑟菌 (GC) 是一个日益严重的公共卫生问题，由于感染人数的增加，该问题可能会进一步恶化。 抗生素耐药性和缺乏疫苗。已知 IV 型菌毛 (Tfp) 对于 GC 毒力至关重要 人类，并且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。然而， 负责高亲和力粘附的特定 GC 蛋白和宿主受体的身份并不相同 已知。二十年已发表的实验有力地支持了低丰度蛋白质的假设 PilC 是 GC Tfp 呈现的高亲和力粘附素。然而，人们对它的整体结构知之甚少。 PilC、它与 Tfp 结合的机制以及它可能参与的宿主受体。 在这个项目中，我们将使用体内基因测试和体外生化分析来测试PilC模型 职能组织，我们将使用由此产生的信息和试剂来开始以下过程： 识别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与菌毛的关联机制，PilC影响菌毛的机制 生物发生，以及 GC 和密切相关的病原体脑膜炎奈瑟氏菌粘附的机制 人类上皮组织启动感染。