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. burgdorferi results 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.
Because of its importance
as a human and animal pathogen and the value of complete genome
sequence information for understanding its life cycle and advancing
drug and vaccine development, TIGR sequenced the genome of the
type strain (B31) for B. burgdorferi using the random sequencing
method previously described (Fleischmann et al., 1995; Fraser
et al., 1995; Bult et al., 1996; Tomb et al., 1997). The isolate
of B. burgdorferi 31 used for this project contains a total
of 12 linear and 9 circular plasmids.