HUMAN IGG SUBCLASS-SPECIFIC BACTERIAL BINDING PROTEINS

人 IGG 亚类特异性细菌结合蛋白

• 批准号: 3145251
• 负责人: MICHAEL D. BOYLE
• 金额: $ 15.39万
• 依托单位: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-01 至 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3145251
• 关键词: Streptococcus infection; Streptococcus pyogenes; bacterial proteins; binding proteins; chickens; gene expression; genetic transduction; glomerulonephritis; host organism interaction; human tissue; immune complex; immunoglobulin G; immunoglobulin genes; laboratory mouse; molecular cloning; nucleic acid probes; protein structure function; recombinant proteins; serology /serodiagnosis; site directed mutagenesis; virulence

The focus of the proposed studies is to develop a detailed classification for type II IgG-binding proteins expressed by group A streptococci and to understand the role of these molecules in streptococcal infection or post-infection sequelae. The initial focus will be to develop serological and gene probes to analyze the qualitative and quantitative expression of different forms of IgG-binding protein(s) expressed by group A strains. Once a detailed classification system has been established, these techniques will be applied to characterize the type II IgG-binding proteins expressed on fresh clinical isolates of group A streptococci in order to determine whether there is an association between the qualitative or quantitative expression of IgG-binding proteins and the course of infection of post-infection sequelae in the patient from which the strain was recovered. The biological activities of IgG-binding proteins will be explored using a variety of in vitro and in vivo assay systems. These studies will involve group A strains with defined IgG-binding protein expression as well as examining the effect of insertion of type II IgG-binding protein gene(s) into an IgG-binding protein negative S. gordonii Challis strain. The in vitro system will measure the ability of bacteria expressing type II IgG-binding proteins to survive in human blood while the in vivo system will focus on the ability of the bacteria to establish lethal infections when injected into the skin of mice. These studies will be designed to document the importance of expression of type II IgG-binding proteins. The potential role for an M protein IgG-binding protein hybrid molecule in the formation of immune complexes that could contribute to post-streptococcal glomerulo-nephritis will also be examined. Taken together, these studies of type II IgG-binding proteins should yield new information on the diversity of these molecules and their potential role in establishing invasive streptococcal infections as well as their possible contributions to post-infection sequelae.

拟议研究的重点是制定详细的分类 对于A组链球菌表达的II型IgG结合蛋白， 了解这些分子在链球菌感染中的作用， 感染后后遗症 最初的重点将是发展 血清学和基因探针进行定性和定量分析， 表达不同形式的IgG结合蛋白， A群菌株。 一旦有了详细的分类系统， 建立，这些技术将被应用于表征II型 A组新鲜临床分离株表达的IgG结合蛋白 链球菌以确定是否存在关联 IgG结合的定性或定量表达 蛋白质和感染后后遗症的感染过程中， 从该菌株中回收的患者。 IgG结合蛋白的生物学活性将使用 各种体外和体内测定系统。 这些研究将 涉及具有确定IgG结合蛋白表达的A组菌株， 以及检测插入II型IgG结合蛋白的作用 基因转化为IgG结合蛋白阴性S.戈登氏查利斯菌株。 体外系统将测量细菌表达型的能力， II IgG结合蛋白在人血液中存活，而在体内 该系统将侧重于细菌建立致命的能力， 当注射到小鼠的皮肤上时， 这些研究报告将 旨在记录II型IgG结合蛋白表达的重要性 proteins. M蛋白IgG结合蛋白杂合体的潜在作用 分子在免疫复合物的形成，可能有助于 还将检查链球菌感染后肾小球肾炎。 采取 总之，这些对II型IgG结合蛋白的研究应该产生新的 关于这些分子的多样性及其潜在作用的信息 在建立侵袭性链球菌感染以及 可能导致感染后后遗症。