ROLE OF SURFACE DEHYDROGENASE IN STREPTOCCAL INFECTION

PI假设表面脱氢酶(SDH)在 通过促进A组进入在感染早期事件中的关键作用 链球菌进入咽部细胞。作者指出SDH是必不可少的 对于GAS的生存，以及SDH有多种方式绑定到几个 哺乳动物蛋白质，也具有ADP核糖化活性。SDH与 哺乳动物咽部细胞及其调控的信号转导通路 咽部细胞，促进宿主细胞的黏附和穿透。 具体目的1.一种32 kDa的SDH咽细胞膜受体 特异靶蛋白的提纯和生化表征2.受体结合 SDH的结构域将使用几种蛋白质和定点进行鉴定 建立SDH-咽部细胞分子基础的诱变技术 受体相互作用。 特定目标3使用完整链球菌和重组天然和突变的SDH 蛋白质，SDH介导的咽部细胞信号通路将是 通过研究各种细胞内信号事件来阐明。 特定目标4，原生和突变的SDH将共价连接到 荧光微球用于研究细胞系的黏附和侵袭。

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.