Comparative Genome Hybridization Reveals Substantial Variation among Clinical Isolates of Borrelia burgdorferi Sensu Stricto with Different Pathogenic Properties

ABSTRACT Clinical and murine studies suggest that there is a differential pathogenicity of different genotypes of Borrelia burgdorferi, the spirochetal agent of Lyme disease. Comparative genome hybridization was used to explore the relationship between different genotypes. The chromosomes of all studied isolates were highly conserved (>93%) with respect to both sequence and gene order. Plasmid sequences were substantially more diverse. Plasmids lp54, cp26, and cp32 were present in all tested isolates, and their sequences and gene order were conserved. The majority of linear plasmids showed variation both in terms of presence among different isolates and in terms of sequence and gene order. The data strongly imply that all B. burgdorferi clinical isolates contain linear plasmids related to each other, but the structure of these replicons may vary substantially from isolate to isolate. These alterations include deletions and presumed rearrangements that are likely to result in unique plasmid elements in many isolates. There is a strong correlation between complete genome hybridization profiles and other typing methods, which, in turn, also correlate to differences in pathogenicity. Because there is substantially less variation in the chromosomal and circular plasmid portions of the genome, the major differences in open reading frame content and genomic diversity among isolates are linear plasmid driven.

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[109]  S. Casjens,et al.  Linear chromosomes of Lyme disease agent spirochetes: genetic diversity and conservation of gene order , 1995, Journal of bacteriology.

[110]  G. Weinstock,et al.  Physical map of the genome of Treponema pallidum subsp. pallidum (Nichols) , 1995, Journal of bacteriology.

[111]  D. Liveris,et al.  Molecular typing of Borrelia burgdorferi sensu lato by PCR-restriction fragment length polymorphism analysis , 1995, Journal of clinical microbiology.

[112]  B. E. Davidson,et al.  Conservation of gene arrangement and an unusual organization of rRNA genes in the linear chromosomes of the Lyme disease spirochaetes Borrelia burgdorferi, B. garinii and B. afzelii. , 1994, Microbiology.

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[114]  R. C. Johnson,et al.  Comparative analysis of genetic variability among Borrelia burgdorferi isolates from Europe and the United States by restriction enzyme analysis, gene restriction fragment length polymorphism, and pulsed-field gel electrophoresis , 1993, Journal of clinical microbiology.

[115]  R. Lefebvre,et al.  Genetic diversity among Borrelia burgdorferi isolates from wood rats and kangaroo rats in California , 1993, Journal of clinical microbiology.

[116]  R. Marconi,et al.  Variation in the size of the ospA-containing linear plasmid, but not the linear chromosome, among the three Borrelia species associated with Lyme disease. , 1993, Journal of general microbiology.

[117]  A. Barbour,et al.  The cryptic ospC gene of Borrelia burgdorferi B31 is located on a circular plasmid , 1993, Infection and immunity.

[118]  R. Marconi,et al.  Transcriptional analyses and mapping of the ospC gene in Lyme disease spirochetes , 1993, Journal of bacteriology.

[119]  R. Lefebvre,et al.  Characterization of Borrelia burgdorferi isolates by restriction endonuclease analysis and DNA hybridization , 1989, Journal of clinical microbiology.

[120]  A. Barbour,et al.  Plasmid analysis of Borrelia burgdorferi, the Lyme disease agent , 1988, Journal of clinical microbiology.

[121]  A. Spielman,et al.  Duration of tick attachment and Borrelia burgdorferi transmission , 1987, Journal of clinical microbiology.

[122]  A. Steere,et al.  The spirochetal etiology of Lyme disease. , 1983, The New England journal of medicine.