PATHOGENESIS OF INFECTION WITH THE LYME DISEASE SPIROCHETE, BORRELIA BURGDORFERI

我们的总体目标是了解疏螺旋体 伯氏杆菌建立了一种感染：扁虱之间的传播循环 媒介和哺乳动物的宿主，这两者都是维持 自然界中的螺旋体。以下是与此相关的研究工作 进球。 L。外表面蛋白变异。伯氏杆菌的外膜 包含几种丰富的蛋白质(OSP)，它们的大小和 和未知函数的表达式。很可能不同的操作系统 赋予螺旋体不同的与 它必须在不同的环境中生存。罗莎和霍根 在自然界中鉴定的DSP基因之间的同源重组 壁虱中伯氏伯氏杆菌的种群。马戈利斯博士还确定了 转录调控或信使核糖核酸稳定性负责 不同克隆变异体的OSP合成模式不同。他已经克隆了 一种在伯氏杆菌培养中可变表达的OSP基因， 研究参与ITS调控的序列和因素 表情。 2.线形质粒复制。对异常线性的理解 疏螺旋体染色体和质粒的结构具有内在的意义 和实用的优点。蒂利博士已经分离出热休克基因的同源物 它们参与了其他系统中的质粒复制。这些基因是 由温度上移引起的，在转移时会经历 从扁虱到哺乳动物。她已经分离并测序了这种病毒的基因。 疏螺旋体IHF同源基因，另一个可能参与 线性质粒复制，并对其生物学特性进行了研究 在大肠杆菌中的活性。她已经确定了独一无二的连带或 可以代表复制的线形质粒的环状形式 中间体。

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.