The Genetic Basis of Borrelia Burgdorferi Variations in Human Invasiveness and Enzootic Prevalence Through Complete Genome Sequencing and Comparative Genomics

Strains

For this project, 11 strains of B. burgdorferi as well as 6 other Borrelia species will be sequenced. For project status, please see the production status page.

Background

In the mid-1970s, a geographic clustering of an unusual rheumatoid arthritis-like condition was reported in Connecticut. This syndrome, Lyme disease, proved to be a newly recognized disorder characterized by some or all of the following mainfestations: an initial erythematous annular rash, flu-like symptoms, neurologic complications, and arthritis in about 50% of untreated patients. In the United States, the disease occurs primarily in three geographic regions including the Northeast, Midwest, and far western parts of California and Oregon These areas include the ranges of various species of Ixodes ticks, the primary vector of Lyme disease. Lyme disease is now the most common tick-transmitted illness in the United States and has also been reported in other parts of the Northern hemisphere, particularly in western Europe.

In the early-1980s, a novel spirochete, called Borrelia burgdorferi, was isolated and cultured from the mid-gut of Ixodes ticks, and subsequently from patients with Lyme disease. B. burgdorferi resembles other spirochetes in that it is a highly specialized, motile, two-membrane, spiral-shaped bacteria which lives primarily as an extracellular pathogen. One of the most striking features of B. burgdorferi as compared with other eubacteria is its unusual genome, which includes a linear chromosome approximately one megabase in size and numerous linear and circular plasmids. Long-term culture of B. burgdorferiresults in a loss of some plasmids and changes in expressed protein profiles. Associated with the loss of plasmids is a loss in the ability of the organism to infect laboratory animals, suggesting that the plasmids encode key genes involved in virulence.

B. burgdorferi may persist in humans and animals for months or years following initial infection, despite a robust humoral immune response. B. burgdorferi is susceptible to antibiotics in vitro, however, there are contradictory reports as to the efficacy of antibiotics in vivo. Consequently, considerable attention has focused on the development of a vaccine for Lyme disease. Current evidence suggests humoral immunity plays an important role in prevention of infection and resolution of disease; however, one of the difficulties in developing a meaningful strategy for immunization is that it is not understood what aspects of humoral and cell-mediated immunity are required to counter established infection.