Bdr proteins and Borrelia pathogenesis

Bdr 蛋白和疏螺旋体发病机制

• 批准号: 6465437
• 负责人: RICHARD T MARCONI
• 金额: $ 32.75万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-15 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6465437
• 关键词: Borrelia; Lyme disease; antibacterial antibody; bacteria infection mechanism; bacterial genetics; bacterial proteins; gel mobility shift assay; gene expression; gene induction /repression; genetic regulation; genetic transcription; host organism interaction; laboratory mouse; laboratory rabbit; life cycle; microorganism growth; mutant; plasmids; polymerase chain reaction; ticks; western blottings

While evidence suggests that plasmid encoded proteins are key in understanding the host-pathogen interaction in Borrelia infections, the functions for most of these proteins remain undefined. Since the plasmid carried genes are largely unique to the Borrelia, it is likely that they hold the key to understanding the unique attributes of Borrelia biology and pathogenesis. The bdr gene family is a large, polymorphic, plasmid carried gene family carried and expressed by all species of the genus. In Borrelia burgdorferi B31MI the gene family contains 18 members distributed among the linear and circular plasmids. We have demonstrated that the Bdr proteins are organized into distinct sub-families, are associated with the inner membrane, and are differentially expressed in response to environmental conditions. In this application we present a strategy for defining the expression patterns of the Bdr proteins in different environments, elucidating the mechanisms involved in their regulation, and for testing the effects of Bdr gene inactivation on Borrelia pathogenesis.

虽然证据表明质粒编码的蛋白是理解疏螺旋体感染中宿主 - 病原体相互作用的关键，但大多数这些蛋白质的功能仍然不确定。 由于质粒携带的基因在很大程度上是伯氏菌所独有的，因此它们很可能是理解伯氏生物学和发病机理的独特属性的关键。 BDR基因家族是一个大型，多态的质粒，载有基因家族，并由该属的所有物种携带和表达。 在Borrelia burgdorferi B31MI中，基因家族包含18个成员，分布在线性和圆形质粒之间。 我们已经证明，BDR蛋白被组织成不同的亚菌群，与内膜有关，并根据环境条件的响应差异表达。 在此应用中，我们提出了一种在不同环境中定义BDR蛋白的表达模式的策略，阐明了其调节所涉及的机制，并测试BDR基因失活对伯雷利亚发病机理的影响。