Lyme Genome

Lyme disease is a debilitating bacterial infection transmitted by bite of the Ixodes scapularis tick. The disease takes its name from Lyme, Connecticut, where the disease was described in 1975. The infectious eagent was subseuquently identified as B. burgdorferi. The disease primarily affects people living in the northeastern and upper north-central United States, and along the northern Pacific Coast.

All four stages of Ixodes scapularis, the black-legged or deer tick with dime for size comparison.

B. burgdorferi was sequenced by scientists at the same research group, The Institute for Genomic Research (TIGR), where the genomes of  the bacterium Haemophilus influenzae and the ulcer-causing Heliocobacter pylori were sequenced. The researchers used software programs that allowed rapid and accurate sequencing of large segments of DNA. The so-called 'shot-gun sequencing strategy' begins with the preparation of a single random DNA fragment library by first mechanically breaking the organism apart. The resulting fragments are then sequenced and assembled to produce the complete genome with the help of software programs.

The genome of Borrelia burgdorferi contains a linear chromosome of 910,725 bp and 19 linear and circular plasmids with a combined size of more than 560,000 bp.  The chromosome contains 853 genes encoding a basic set of proteins for DNA replication, transcription, translation, solute transport, and energy metabolism, but no genes for cellular biosynthetic reactions. Greater than 85% of the plasmid genes have no known biological function; thirty-nine percent of plasmid genes are paralogs that comprise 47 gene families.

The biological significance of the multiple plasmid-encoded genes is not clear, although they may play a role in antigenic variation or immune evasion. Long-term passage of B. burgdorferi in vitro results in a loss of some circular and linear plasmids, changes in expressed protein profiles and a loss in the ability of the organism to infect laboratory animals, suggesting that the plasmids encode key genes involved in virulence.

With the exception of a small number of putative virulence genes, this organism contains few recognizable genes involved in virulence or host-parasite interactions. This suggests that B. burgdorferi differs from better-studied eubacteria in this respect. Determining the biological role of the multi-copy plasmid-encoded genes will be of great interest, in light of previous work implicating plasmid genes in infectivity and virulence.  In addition, the finding of more than 100 lipoproteins in B. burgdorferi may result in identification of novel targets for vaccine development, the researchers report.

The B. burgdorferi organism can persist in humans and animals for months or years following initial infection, despite a robust immune response. Treatment with antibiotics immediately after transmission can halt the infection, but left untreated the disease can progress to a crippling arthritis.

Researchers are anxious to develop a vaccine for Lyme disease.  A canine vaccine consisting of whole inactivated organisms has been available since the early 1990s, however, the success of this vaccine in protecting dogs against B. burgdorferi infection has been mixed.  Human clinical trials of a vaccine derived from recombinant outer surface proteins of B. burgdorferi are also underway.

One of the difficulties in developing a meaningful strategy for immunization is the fact that it is not at all clear what roles humoral and cell-mediated immunity play in the pathogenesis of and protection against acute and chronic Lyme disease. The researchers hope the genomic information will contribute to the search for vaccines and treatments for Lyme disease. One possible first step would be the development of a culture method for the bacterium.

On a more general level, the sequencing of B. burgdorferi raises questions about the structure of bacterial chromosomes. In particular, researchers will be looking at differences and similarities between plasmids and chromosomes within the genome. The research could also lead to better understanding of bacterial evolution in general.

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