Outer surface protein gene expression in B. burgdorferi

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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.