Studies on the glycosylation of P. aeruginosa pili

铜绿假单胞菌菌毛糖基化的研究

• 批准号: 6456356
• 负责人: PETER A. CASTRIC
• 金额: $ 5.23万
• 依托单位: DUQUESNE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-15 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6456356
• 关键词: Pseudomonas aeruginosa; bacteria infection mechanism; bacterial genetics; bacterial somatic antigen; bacterial vaccines; cell component structure /function; chromatography; gene expression; glycosylation; host organism interaction; intermolecular interaction; lipopolysaccharides; molecular site; nuclear magnetic resonance spectroscopy; pilin; pilus; posttranslational modifications; protein biosynthesis; protein localization; protein structure function; proteoglycan; site directed mutagenesis; southern blotting; vaccine development; virulence; western blottings

DESCRIPTION (provided by the applicant): Pseudomonas aeruginosa persists as a major cause of life-threatening infections for individuals with the following conditions: cystic fibrosis, burns, wounds, cancer (leukemias), those receiving immunosuppressive therapy, diabetics, as well as intravenous drug users. The pili of this bacterium are protein filaments that extend from the ends of the cell. These structures serve as adhesion factors, and so are important virulence factors. The long-term objectives of this project are to determine the role of pilus glycosylation in P. aeruginosa pathogenesis and to ascertain the importance of the glycan in pilus vaccine design. Work from my laboratory has shown that the pili of P. aeruginosa 1244 are glycosylated with a trisaccharide moiety originating in the lipopolysaccharide O-antigen biosynthetic pathway. The research in this proposal aims to determine the structural relationship between the pilin glycan and the O-antigen. In addition, it will explore the ability of the glycosylation system to attach heterologous glycan to pilin. The project will determine the glycan precursor involved in pilin glycosylation and elucidate the point in pilus biogenesis where glycosylation occurs. The project will determine the step in O-antigen biosynthesis that produces the glycan and the subcellular location of pilin glycosylation.

描述(申请人提供)：铜绿假单胞菌作为 以下是危及生命的个人感染的主要原因 病情：囊性纤维化，烧伤，伤口，癌症(白血病)，接受 免疫抑制疗法、糖尿病患者以及静脉注射吸毒者。这个 这种细菌的菌毛是从细菌末端延伸出来的蛋白质细丝。 手机。这些结构起着粘合因子的作用，因此很重要。 毒力因素。该项目的长期目标是确定 菌毛糖基化在铜绿假单胞菌发病机制中的作用 葡聚糖在菌毛疫苗设计中的重要性。在我的实验室工作 已经表明，铜绿假单胞菌1244的菌毛是由糖基化的 三糖部分起源于内毒素O-抗原 生物合成途径。这项建议中的研究旨在确定 菌毛多聚糖与O-抗原的结构关系。在……里面 此外，它还将探索糖基化系统连接的能力 异源葡聚糖到菌毛素。该项目将确定葡聚糖前体 参与菌毛糖基化并阐明其在菌毛生物发生中的作用 发生糖基化的地方。该项目将决定O-抗原的步骤 产生多聚糖的生物合成和毛细蛋白的亚细胞定位 糖基化。