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，是由螺旋体伯氏伯氏菌（Borrelia Burgdorferi）感染引起的。 B. burgdorferi合成了几种外表面蛋白（OSP），包括OSPA，OSPB和OSPC。 OSPA是莱姆病疫苗的靶标，被认为与B. burgdorferi与其tick载体的肠道结合涉及。 OSPC被认为是一种传播或哺乳动物的定殖因子，其合成在滴答过程中被诱导。 OSPA和OSPB与OSPC的变化可能是B. Burgdorferi适应tick矢量和哺乳动物宿主的不同环境的一种手段，并为环境过渡做准备。我们的假设是，DNA超串联感知环境信号并将其转换为一个改变的基因表达程序，其中OSPC转录直接受DNA超螺旋的影响。该项目建议使用分子遗传和生化技术解剖外表面蛋白基因表达的调节。 GAC和HBB是两个建筑DNA结合蛋白，它们在B. bugdorferi中改变了DNA结构和超螺旋。我们将通过遗传分析GAC和HBB在OSPC转录中的作用，通过突变B.burgdorferi中的GAC和HBB基因。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。我们认为，我们将能够探测伯格多菲利（B. burgdorferi）外表面蛋白基因表达变异的机制，这将有助于理解该病原体的基本生物学，并可以改善诊断，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