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Journal of Bacteriology, July 2006, p. 4879-4889, Vol. 188, No. 13
0021-9193/06/$08.00+0     doi:10.1128/JB.00229-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Transcriptional Regulation of the Borrelia burgdorferi Antigenically Variable VlsE Surface Protein

Tomasz Bykowski,¹ Kelly Babb,^1, Kate von Lackum,¹ Sean P. Riley,¹ Steven J. Norris,² and Brian Stevenson^1*

Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky 40536-0298,¹ Department of Microbiology and Molecular Genetics, University of Texas Medical School at Houston, Houston, Texas 77225-0708²

Received 13 February 2006/ Accepted 12 April 2006

The Lyme disease agent Borrelia burgdorferi can persistently infect humans and other animals despite host active immune responses. This is facilitated, in part, by the vls locus, a complex system consisting of the vlsE expression site and an adjacent set of 11 to 15 silent vls cassettes. Segments of nonexpressed cassettes recombine with the vlsE region during infection of mammalian hosts, resulting in combinatorial antigenic variation of the VlsE outer surface protein. We now demonstrate that synthesis of VlsE is regulated during the natural mammal-tick infectious cycle, being activated in mammals but repressed during tick colonization. Examination of cultured B. burgdorferi cells indicated that the spirochete controls vlsE transcription levels in response to environmental cues. Analysis of PvlsE::gfp fusions in B. burgdorferi indicated that VlsE production is controlled at the level of transcriptional initiation, and regions of 5' DNA involved in the regulation were identified. Electrophoretic mobility shift assays detected qualitative and quantitative changes in patterns of protein-DNA complexes formed between the vlsE promoter and cytoplasmic proteins, suggesting the involvement of DNA-binding proteins in the regulation of vlsE, with at least one protein acting as a transcriptional activator.

Present address: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907.

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