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Updated: Aug 30, 2026

Phage-Mediated Genetic Manipulation of the Lyme Disease Spirochete Borrelia burgdorferi
Published on: September 28, 2022
Intra- and interbacterial genetic exchange of Lyme disease spirochete erp genes generates sequence identity amidst
Brian Stevenson1, Jennifer C Miller
1Department of Microbiology, Immunology, and Molecular Genetics, MS415 Chandler Medical Center, University of Kentucky College of Medicine, Lexington, KY 40536-0298, USA. bstev0@uky.edu
Abstract:
All isolates of the spirochete Borrelia burgdorferi contain multiple, different plasmids of the cp32 family, each of which contains a locus encoding Erp surface proteins. Many of these proteins are known to bind host complement regulatory factor H, enabling the bacteria to avoid killing by the alternative complement pathway during vertebrate infection. In the present study, we characterized the erp loci and cp32 plasmids of strains N40, Sh-2-82, and 297 and compared them to the previously determined cp32 sequences of type strain B31. Bacteria of strain N40 contain 6 different cp32s, those of Sh-2-82 contain 10, and 297 bacteria contain 9 cp32s. Significant conservation between all strains was noted for the cp32 loci responsible for plasmid maintenance, indicating close relationships that appear to correspond with incompatibility groups. In contrast, considerable diversity was found between erp gene sequences, both within individual bacteria and between different strains. However, examples of identities among erp loci were found, with strains Sh-2-82, 297, and B31 each containing three identical loci that likely arose through intrabacterial genetic rearrangements. These studies also found the first evidence of large-scale genetic exchanges between Lyme disease spirochetes in nature, including the apparent transfer of an entire cp32 plasmid between two different bacteria.
Insights
Borrelia burgdorferi spirochetes utilize cp32 plasmids encoding Erp proteins to evade host defenses. This study reveals significant diversity in Erp genes but conservation in plasmid maintenance, alongside evidence of large-scale plasmid exchange in nature.
Area of Science:
- Microbiology
- Genetics
- Immunology
Background:
- Borrelia burgdorferi, the causative agent of Lyme disease, possesses multiple cp32 plasmids encoding Erp surface proteins.
- Erp proteins facilitate immune evasion by binding complement factor H, inhibiting the alternative complement pathway.
- Understanding the genetic diversity and dynamics of these plasmids is crucial for comprehending bacterial pathogenesis.
Purpose of the Study:
- To characterize the cp32 plasmids and associated erp loci in Borrelia burgdorferi strains N40, Sh-2-82, and 297.
- To compare these genetic elements with those of the type strain B31.
- To investigate the extent of genetic diversity and potential for horizontal gene transfer among these plasmids.
Main Methods:
- Comparative sequence analysis of cp32 plasmids and erp loci from different Borrelia burgdorferi strains.
- Identification and characterization of plasmid maintenance loci.
- Analysis of erp gene sequence diversity and identification of identical loci.
Main Results:
- Strains N40, Sh-2-82, and 297 harbor 6, 10, and 9 distinct cp32 plasmids, respectively.
- Conserved cp32 loci involved in plasmid maintenance suggest close phylogenetic relationships and incompatibility groups.
- High diversity was observed in erp gene sequences within and between strains, with instances of identical loci suggesting intrabacterial rearrangements.
- Evidence for large-scale genetic exchange, including the transfer of entire cp32 plasmids, was identified between Lyme disease spirochetes in natural settings.
Conclusions:
- The cp32 plasmid family in Borrelia burgdorferi exhibits both conserved elements for maintenance and highly diverse erp genes for immune evasion.
- Intrabacterial genetic rearrangements and horizontal plasmid transfer are significant mechanisms shaping the genetic landscape of these spirochetes.
- These findings provide novel insights into the evolution and adaptability of Borrelia burgdorferi, impacting our understanding of Lyme disease pathogenesis.
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