PATHOGENESIS OF INFECTION WITH THE LYME DISEASE SPIROCHETE, BORRELIA BURGDORFERI

我们的主要目标是了解疏螺旋体 伯氏螺旋体建立感染：蜱虫之间的传播周期 载体和哺乳动物储库宿主，这两者都需要维持 自然界中的螺旋体以下研究工作与此有关 目标. L.外表面蛋白变异。 B的外膜burgdorferi 含有几种丰富的蛋白质（Osps），其大小可变， 表达和未知的功能。很可能不同的OSP 赋予螺旋体不同的特性， 不同的生存环境。罗莎和霍根 在自然界中鉴定的DSP基因之间的同源重组 B种群。蜱虫中的伯氏菌。马戈利斯医生还确定 转录调节或mRNA稳定性是导致 克隆变体之间的Osp合成的不同模式。他克隆了 在B中表达的osp基因。Burgdorferi在文化和是 研究参与其调节的序列和因素， 表情 2.线性质粒复制。 对不寻常的线性的理解 疏螺旋体染色体和质粒的结构是内在的利益 和实际价值。蒂利博士分离出了热休克基因的同源物 在其他系统中参与质粒复制。这些基因 由转移时经历的温度升高引起 从蜱虫到哺乳动物她已经分离并测序了 疏螺旋体IHF同源物，另一个可能参与 线性质粒复制，并表征其生物学特性 活动在E. 杆菌 她已经确定了独特的串联或 代表复制的环状线性质粒 中间体的

Our broad objective is to understand the means by which Borrelia burgdorferi establishes an infection:transmission cycle between the tick vector and mammalian reservoir host, both of which are needed to maintain the spirochete in nature. The following research efforts relate to this goal. l. Outer surface protein variation. The outer membrane of B. burgdorferi contains several abundant proteins (Osps) that are variable in size and expression and of unknown function. It is likely that the different Osps confer distinct properties on the spirochete that are pertinent to the disparate environments in which it must survive. Rosa and Hogan have identified homologous recombination between DSP genes in natural populations of B. burgdorferi in ticks. Dr. Margolis has also determine that transcriptional regulation or mRNA stability is responsible for different patterns of Osp synthesis among clonal variants. He has cloned an osp gene that is variably expressed in B. burgdorferi in culture and is investigating the sequences and factors involved in the regulation of its expression. 2. Linear plasmid replication. An understanding of the unusual linear structure of the Borrelia chromosome and plasmids is of intrinsic interest and practical merit. Dr. Tilly has isolated homologs of heat shock genes that are involved in plasmid replication in other systems. These genes are induced by a temperature upshift as would be experienced upon transfer from a tick to a mammal. She has isolated and sequenced the gene of the Borrelia IHF homolog, another candidate gene that may be involved in linear plasmid replication, and is characterizing its biological activities in E. coli. She has identified unique concatemeric or circular forms of the linear plasmids that could represent replication intermediates.