Molecular Sleuthing with the Lyme Disease Agent

Abstract

Borrelia burgdorferi, the spirochete that causes Lyme disease, is an obligate parasite of both its tick vector and mammalian or avian host. This bipartite lifestyle demands the ability to sense and to adapt in order to stay alive and move between these two different environments and persist in nature. A major focus of our research has been the development and application of a genetic system for B. burgdorferi, in order to investigate, at the molecular level, the roles of specific spirochetal components at different stages of the infectious cycle. Part of this endeavor has been an investigation of the structure and function of the unusual segmented genome of B. burgdorferi, both in terms of utility as genetic tools and as a biological role in infection. It would be misleading to argue that this research is designed to have a direct impact on the diagnosis, treatment, or prevention of Lyme disease. However, B. burgdorferi is a wide spread human pathogen and our research has contri­buted to a better understanding of how this tick-borne pathogen infects a mammalian host. The genetic system that we have develo­ped facilitates not only the study of the Lyme disease spirochete by a number of labs, but has also provided gui­dance for the development of genetic tools in other pathogenic bacteria. The basic mechanisms underlying the genomic structure of B. burgdorferi have broader applicability in molecular biology. Finally, determining the roles of specific B. burgdorferi components in the tick vector and mammalian host will contribute to our understanding of the infectious strategy of this and other vector-borne pathogens.