PATHOGENESIS OF INFECTION WITH THE LYME DISEASE SPIROCHETE, BORRELIA BURGDORFERI

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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.