Studies into the Mechanism of Borrelia Burgodorferi vlsE Recombination

The causative agent of Lyme disease, Borrelia burgdorferi, can infect humans and other animals for many years, perhaps even a lifetime. It is thought that the bacteria's vis system plays an important role in longterm infection. During infection, the DNA sequence of the bacteria's vIsE gene changes, due to replacement of certain DNA sequences with others supplied from elsewhere in the bacteria's genome. The mechanism by which this occurs is not yet known, but its identification will be an important step toward understanding the ability of this pathogen to infect humans and will lead to improved, novel therapies for treatment of Lyme disease. We have discovered that B. burgdorferi makes at least one protein that binds to a specific region of DNA in the vIsE gene. We propose that this protein plays an important role in visE recombination. In this proposal, we outline studies to identify this protein(s) and precisely define the DNA sequence within vIsE that binds the protein(s), then develop mutant bacteria that will permit examinations of the effects that preventing protein-DNA interactions have upon vIsE recombination.