Lyme disease is a multisystem, tick-borne chronic infection caused by the persistence of the spirochete Borrelia burgdorferi. B. burgdorferi has the ability to proliferate in a variety of niches in reservoir and human hosts as well as in the vector lxodes scapularis. Preliminary evidence indicates that differential gene expression resulting from environmental stimuli in one of the mechanisms that allows bacterial to adapt rapidly to fast changing environments found during infection and disease of vectors and hosts. We and others have described a family of chromosomal genes (bmpA-D) encoding homologous 36.9-39.8 kDa lipoproteins of the p39 family. The tandem chromosomal location of the bmp genes, their homology and overlapping regulatory signals together with the potential surface location of the proteins they encode in addition to their apparent up regulation by environmental stimuli suggests the hypothesis that these proteins may be important for B. burgdorferi survival in different environments. In this project, we propose to study the effects environmental stimuli have on bmpC, a member of this gene family first described by us, both in vitro and in vivo in mice and ticks, in an effort to improve our understanding of the mechanisms employed by B. burgdorferi to enable it to persist and thrive in vectors and hosts. The long-range goal of our efforts is to improve understanding of B. burgdorferi gene expression despite the lack of genetic systems that would facilitate this work.
The specific aims of the current project are: 1) identify anti-BmpC Mab and polyclonal antibodies not cross-reactive with BmpD, BmpA and BmpB and use them to characterize BmpC protein and confirm its localization and lipidation in B. burgdorferi 297; 2) Determine levels of expression and mechanisms of regulation of bmpC under different in vitro and in vivo conditions; and 3) Determine genetic organization and DNA structural and regulatory sequences of bmpC in B. burgdorferi, B. afzelii and B. garinii genospecies and in B. burgdorferi 297 grown under different conditions in vitro and in vivo. The latter studies will indicate whether different levels of transcription are secondary to changes in the regulatory and structural DNA sequences of the bmpC gene.
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