Outer surface protein gene expression in B. burgdorferi

伯氏疏螺旋体外表面蛋白基因表达

• 批准号: 6556171
• 负责人: D. SCOTT SAMUELS
• 金额: $ 14万
• 依托单位: UNIVERSITY OF MONTANA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-15 至 2005-05-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6556171
• 关键词: Borrelia; DNA binding protein; DNA footprinting; DNA gyrase; Lyme disease; bacterial genetics; bacterial proteins; biological signal transduction; gel mobility shift assay; gene environment interaction; gene expression; gene mutation; genetic promoter element; genetic regulation; genetic transcription; intermolecular interaction; kanamycin; membrane proteins; nucleic acid structure; protein biosynthesis; protein sequence; site directed mutagenesis; streptomycin; surface antigens; temperature

DESCRIPTION (provided by applicant): Lyme disease, the most common arthropod-borne disease in the United States, is caused by infection with the spirochete Borrelia burgdorferi. B. burgdorferi synthesizes several outer surface proteins (Osps), including OspA, OspB and OspC. OspA is the target in the Lyme disease vaccine and is thought to be involved in the binding of B. burgdorferi to the gut of its tick vector. OspC is thought to be a transmission or mammalian colonization factor and its synthesis is induced during tick feeding. The variation of OspA and OspB versus OspC is likely a means by which B. burgdorferi adapts to the different environments of the tick vector and mammalian host, and prepares for the environmental transition. Our hypothesis is that DNA supercoiling senses environmental signals and transduces them into an altered gene expression program in which ospC transcription is directly affected by DNA supercoiling. This project proposes to dissect, using molecular genetic and biochemical techniques, the regulation of outer surface protein gene expression. Gac and Hbb are two architectural DNA-binding proteins that alter DNA structure and supercoiling in B. burgdorferi. We will genetically assay the role of Gac and Hbb in ospC transcription by mutating the gac and hbb genes in B.burgdorferi. In addition, we will define cis-acting sequences by constructing ospC promoter mutants. We believe that we will be able to probe the mechanism of the variation in outer surface protein gene expression in B. burgdorferi, which will contribute to the understanding of the basic biology of this pathogen and can lead to improved diagnostic, prevention and treatment strategies.

描述（由申请人提供）：莱姆病是美国最常见的节肢动物传播疾病，由伯氏疏螺旋体螺旋体感染引起。伯氏疏螺旋体合成多种外表面蛋白 (Osp)，包括 OspA、OspB 和 OspC。 OspA 是莱姆病疫苗的靶标，被认为参与伯氏疏螺旋体与其蜱载体肠道的结合。 OspC 被认为是一种传播因子或哺乳动物定植因子，其合成是在蜱进食过程中诱导的。 OspA 和 OspB 相对于 OspC 的变异可能是伯氏疏螺旋体适应蜱媒介和哺乳动物宿主不同环境并为环境转变做好准备的一种手段。我们的假设是 DNA 超螺旋感知环境信号并将其转变成改变的基因表达程序，其中 ospC 转录直接受到 DNA 超螺旋的影响。该项目拟利用分子遗传学和生化技术来剖析外表面蛋白基因表达的调控。 Gac 和 Hbb 是两种结构性 DNA 结合蛋白，可改变伯氏疏螺旋体的 DNA 结构和超螺旋。我们将通过突变伯氏疏螺旋体中的 gac 和 hbb 基因，从遗传学角度分析 Gac 和 Hbb 在 ospC 转录中的作用。此外，我们将通过构建 ospC 启动子突变体来定义顺式作用序列。我们相信，我们将能够探讨伯氏疏螺旋体外表面蛋白基因表达变异的机制，这将有助于了解该病原体的基础生物学，并可以改进诊断、预防和治疗策略。

项目成果

parC mutations in fluoroquinolone-resistant Borrelia burgdorferi.

氟喹诺酮耐药伯氏疏螺旋体中的 parC 突变。

• DOI: 10.1128/aac.49.10.4354-4357.2005
• 发表时间: 2005
• 期刊: Antimicrobial agents and chemotherapy
• 影响因子: 4.9
• 作者: Galbraith,KendalM;Ng,AmandaC;Eggers,BetsyJ;Kuchel,CraigR;Eggers,ChristianH;Samuels,DScott
• 通讯作者: Samuels,DScott