ROLE OF SURFACE DEHYDROGENASE IN STREPTOCCAL INFECTION

表面脱氢酶在链球菌感染中的作用

• 批准号: 6631999
• 负责人: VIJAY PANCHOLI
• 金额: $ 25.87万
• 依托单位: PUBLIC HEALTH RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6631999
• 关键词: Streptococcus pyogenes; bacteria infection mechanism; bacterial proteins; biological signal transduction; cell adhesion; enzyme activity; epithelium; fluorescent dye /probe; gene mutation; glyceraldehyde 3 phosphate dehydrogenase; microorganism metabolism; protein structure function; receptor binding; recombinant proteins; site directed mutagenesis; surface antigens; tissue /cell culture

The PI hypothesizes that a surface dehydrogenase (SDH) plays a critical role in the early events of infection by facilitating entry of group A streptococcus into pharyngeal cells. The author states that SDH is essential for survival of GAS and that SDH has multiple means of binding to several mammalian proteins and also has ADP-ribosylating activity. SDH interacts with mammalian pharyngeal cells and regulates the signal transduction pathways in pharyngeal cells which facilitates adherence and penetration of the host cell. Specific Aim 1. A 32 kDa pharyngeal cell membrane receptor for SDH will be purified and biochemically characterized Specific Aim 2. The receptor binding domain of SDH will be identified using several protein and site directed mutagenesis techniques to establish the molecular basis of SDH-pharyngeal cell receptor interaction. Specific Aim 3 Using intact streptococci and recombinant native and mutated SDH proteins, SDH mediated signaling pathways in pharyngeal cells will be elucidated by studying various intracellular signaling events. Specific Aim 4, native and mutated SDH will be covalently linked to fluorescinated microbeads to study adherence and invasion of cell lines.

PI假设表面脱氢酶（SDH）起作用， 通过促进A组进入，在早期感染事件中起关键作用 进入咽部细胞。作者指出SDH是必不可少的 对于GAS的生存，SDH具有多种结合几种 哺乳动物蛋白质，并且还具有ADP-核糖基化活性。SDH与 哺乳动物咽细胞和调节信号转导途径， 咽细胞，其促进宿主细胞的粘附和穿透。 具体目标1。一种32 kDa的SDH咽细胞膜受体将被发现。 纯化并生化表征特异性目标2。受体结合 SDH的结构域将使用几种蛋白质和定点 诱变技术建立SDH-咽细胞的分子基础 受体相互作用 具体目标3使用完整链球菌和重组天然和突变SDH 蛋白质，SDH介导的信号通路在咽细胞将是 通过研究各种细胞内信号事件来阐明。 特异性目标4，天然和突变的SDH将共价连接至 荧光微珠来研究细胞系的粘附和侵袭。