MOLECULAR ANALYSIS OF T PALLIDUM MEMBRANE PROTEINS

T Pallidum 膜蛋白的分子分析

• 批准号: 2671709
• 负责人: MICHAEL V. NORGARD
• 金额: $ 48.3万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2671709
• 关键词: Treponema pallidum; adenosinetriphosphatase; bacterial genetics; bacterial proteins; biological signal transduction; carboxypeptidase; chemical binding; chromosome walking; gene induction /repression; glucose receptor; human immunodeficiency virus; laboratory mouse; laboratory rabbit; leukocyte activation /transformation; macrophage; membrane proteins; microorganism immunology; nonblood lipoprotein; operon; pathologic process; protein structure function; syphilis; virus replication

Syphilis is a chronic, sexually transmitted disease of humans caused by the spirochetal bacterium Treponema pallidum. The disease's recent dramatic resurgence, coupled with the recognition that syphilitic genital ulcers facilitate transmission of the human immunodeficiency virus (HIV), underscore the importance of studies to elucidate its complex pathogenesis. The inability to cultivate T. pallidum in vitro and the consequent lack of a genetic exchange system continue to hamper efforts to identify virulence factors potentially influencing the pathogenesis of the disease. This lack of information historically has undermined the rational design of immunological intervention strategies for syphilis. Based upon a number of discoveries made by the PI, we shall continue to focus on elucidating the structure-function relationships of T. pallidum membrane lipoproteins as a means of clarifying the role of T. pallidum membrane biology in host-parasite interactions and immunopathogenesis processes. Accordingly, the Specific Aims of this proposal are: (1) To investigate the biological relevance of our discovery that the 47-kDa major membrane lipoprotein of T. pallidum is a penicillin-binding protein with carboxypeptidase activity; (2) To assess whether the 38-kDa lipoprotein, a homolog of the E. coli glucose/galactose-binding (MglB) protein, is a glucose receptor potentially involved in sensory transduction, and to characterize the newly discovered mgl operon of T. pallidum within the context of syphilis pathogenesis; (3) To examine in vivo and in vitro immune cell activation events promoted by synthetic analogs of T. pallidum lipoproteins; and (4) To investigate whether cell activation by T. pallidum lipoprotein-analogs enhance HIV replication in chronically infected macrophages. The pursuit of these Aims will simultaneously advance our understanding of features of T. pallidum membrane biology relevant to syphilis pathogenesis as well as the molecular constituents which induce salient inflammatory processes that culminate in clinical disease.

梅毒是一种人类慢性性传播疾病，由梅毒引起 螺旋体细菌梅毒螺旋体。 近期该病 戏剧性的复苏，加上人们认识到梅毒生殖器 溃疡有利于人类免疫缺陷病毒（HIV）的传播， 强调研究阐明其复杂性的重要性 发病。 无法在体外培养梅毒螺旋体 由此造成的基因交换系统的缺乏继续阻碍着 确定潜在影响致病机制的毒力因子 疾病。 历史上这种信息的缺乏破坏了 合理设计梅毒免疫干预策略。 根据 PI 的多项发现，我们将继续 重点阐明梅毒螺旋体的结构与功能关系 膜脂蛋白作为阐明梅毒螺旋体作用的一种手段 宿主-寄生虫相互作用和免疫发病机制中的膜生物学 流程。因此，本提案的具体目标是： (1) 研究我们的发现的生物学相关性，即 47-kDa 梅毒螺旋体的主要膜脂蛋白是一种青霉素结合蛋白 具有羧肽酶活性； (2) 评估 38-kDa 是否 脂蛋白，大肠杆菌葡萄糖/半乳糖结合蛋白 (MglB) 的同源物 蛋白质，是一种可能参与感觉的葡萄糖受体 转导，并表征新发现的 T 的 mgl 操纵子。 梅毒发病机制中的梅毒； (3) 审查 合成促进的体内和体外免疫细胞激活事件 梅毒螺旋体脂蛋白的类似物； (4) 研究细胞是否 梅毒螺旋体脂蛋白类似物的激活增强了 HIV 复制 慢性感染的巨噬细胞。 追求这些目标将 同时增进我们对梅毒螺旋体特征的理解 膜生物学与梅毒发病机制相关 诱导显着炎症过程的分子成分 最终导致临床疾病。