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The burgeoning molecular genetics of the Lyme disease spirochaete

Key Points

  • Borrelia burgdorferi, the spirochaete that causes Lyme disease, is a fastidious, slow-growing bacterium. This spirochaete has a complex genome composed of multiple linear and circular plasmids, in addition to a linear chromosome.

  • The B. burgdorferi natural life cycle alternates between ticks and small mammals and can be reproduced in the laboratory. Ticks can also be directly infected with B. burgdorferi by several methods.

  • Although genetic studies have only been undertaken in the past ten years, a number of genetic tools have been developed. Multiple selectable markers have been used for gene inactivation by allelic exchange. Shuttle vectors derived from endogenous and broad host-range plasmids have been constructed. A transposon mutagenesis system has been used to inactivate a number of genes.

  • Limitations on genetic studies of B. burgdorferi remain. Transformation frequencies are very low, especially in infectious strains, in part because of plasmid-encoded restriction enzymes. Plasmids are unstable during in vitro growth, so care must be taken to ensure isogenicity of mutant and wild-type strains. Currently, the bacteria are only grown in complex medium, so many nutritional screens and selections are not possible.

  • Despite these limitations, genes affecting a number of functions, including infection of mice or ticks, have been inactivated. Also, a gene that is essential for survival in all conditions has been identified.

Abstract

Lyme disease is the most commonly reported vector-borne disease in North America and Europe, yet we know little about which components of the causative agent, Borrelia burgdorferi, are critical for infection or virulence. Molecular genetics has provided a powerful means by which to address these topics in other bacterial pathogens. Certain features of B. burgdorferi have hampered the development of an effective system of genetic analysis, but basic tools are now available and their application has begun to provide information about the identities and roles of key bacterial components in both the tick vector and the mammalian host. Increased genetic analysis of B. burgdorferi should advance our understanding of the infectious cycle and the pathogenesis of Lyme disease.

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Figure 1: Structure and morphology of Borrelia burgdorferi.
Figure 2: The natural infectious cycle of Borrelia burgdorferi.
Figure 3: The experimental infectious cycle of Borrelia burgdorferi.
Figure 4: Genetic tools for Borrelia burgdorferi.

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Acknowledgements

We thank D. Dorward and E. Fischer for the electron micrographs shown in Figure 1a. We are grateful to N. Charon and S. Goldstein for allowing us to adapt the diagram used in Figure 2c.

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DATABASES

Entrez

Borrelia burgdorferi

Borrelia garinii

cp26

Escherichia coli

flaB

gyrB

Lactococcus lactis

lp25

lp28-1

luxS

pncA

Staphylococcus aureus

Infectious Disease Information

Lyme disease

SwissProt

OspA

OspC

FURTHER INFORMATION

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Rosa, P., Tilly, K. & Stewart, P. The burgeoning molecular genetics of the Lyme disease spirochaete. Nat Rev Microbiol 3, 129–143 (2005). https://doi.org/10.1038/nrmicro1086

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