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Genetic stability of Borrelia burgdorferi recovered from chronically infected immunocompetent mice
D H Persing1, D Mathiesen, D Podzorski
1Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905.
Abstract:
Persistent infection with Borrelia burgdorferi in the presence of a vigorous host immune response has been demonstrated in humans and in animal models of Lyme disease. Long-term persistence of B. burgdorferi was documented recently in our studies of BALB/c and C3H mice infected with cloned and uncloned strains of B. burgdorferi. From mice inoculated with the cloned strain, 11 isolates were recovered from the skin, bladder, and blood after 1 year of infection. Analysis of the genes encoding the major outer surface proteins (OspA and OspB) by restriction digestion and DNA sequencing showed no evidence of point mutations or other small genetic alterations after 1 year. Genomic macrorestriction analysis of whole B. burgdorferi showed no loss or gross alterations of the plasmids encoding OspA, OspB, or OspC. However, in two isolates, loss of a 38-kb plasmid encoding outer surface protein D was noted. Our studies suggest that loss or alteration of the genes encoding OspA and OspB is not a common occurrence during persistent spirochetal infection and that other possible mechanisms, including invasion of immunologically privileged sites, should be actively explored.
Insights
Persistent Borrelia burgdorferi (Lyme disease bacteria) infection in mice showed minimal genetic changes in key outer surface proteins after one year. This suggests other mechanisms, not gene alteration, may enable long-term Lyme disease persistence.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Persistent Borrelia burgdorferi infection, the causative agent of Lyme disease, occurs despite a strong host immune response in both humans and animal models.
- Previous studies have documented long-term persistence of B. burgdorferi.
Purpose of the Study:
- To investigate genetic alterations in Borrelia burgdorferi during persistent infection in a mouse model.
- To determine if changes in genes encoding major outer surface proteins contribute to long-term spirochetal survival.
Main Methods:
- BALB/c and C3H mice were infected with cloned and uncloned strains of B. burgdorferi.
- B. burgdorferi isolates were recovered from various tissues after one year.
- Genetic analysis included restriction digestion, DNA sequencing of OspA and OspB genes, and genomic macrorestriction analysis of plasmids.
Main Results:
- Eleven B. burgdorferi isolates were recovered from mice one year post-infection.
- No point mutations or significant genetic alterations were found in genes for OspA and OspB.
- Plasmids encoding OspA, OspB, and OspC remained largely intact, though a 38-kb plasmid encoding OspD was lost in two isolates.
Conclusions:
- Alterations or loss of genes encoding OspA and OspB are not common mechanisms for persistent Borrelia burgdorferi infection.
- Further research should explore alternative mechanisms, such as invasion of immunologically privileged sites, to explain long-term Lyme disease persistence.