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Dissociation of infectivity and pathogenicity in Borrelia burgdorferi
V Thomas1, J Anguita, S Samanta
1Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Abstract:
Clonal Borrelia burgdorferi N40 (cN40) passaged 75 times in vitro (N40-75) infects mice but does not cause disease. N40-75 passaged 45 times further in vitro (N40-120) was no longer infectious and lacked genes encoded on linear plasmids 38 and 28-1, among other differences. These data suggest that B. burgdorferi cN40, N40-75, and N40-120 have distinct phenotypes that can be used to dissect the genetic elements responsible for pathogenicity and infectivity.
Insights
Clonal Borrelia burgdorferi (cN40) adapted in vitro lost infectivity and pathogenicity. Further passage resulted in the loss of essential genes, highlighting genetic elements crucial for B. burgdorferi virulence.
Area of Science:
- Microbiology and Infectious Diseases
- Bacterial Pathogenesis
- Genetics and Molecular Biology
Background:
- Borrelia burgdorferi is the causative agent of Lyme disease.
- Understanding the genetic basis of B. burgdorferi infectivity and pathogenicity is crucial for developing effective treatments and prevention strategies.
- In vitro passage can alter bacterial virulence and genetic makeup.
Purpose of the Study:
- To investigate the impact of extensive in vitro passaging on the infectivity and pathogenicity of Clonal Borrelia burgdorferi N40 (cN40).
- To identify genetic differences associated with the loss of virulence in passaged B. burgdorferi strains.
- To explore the potential of distinct B. burgdorferi phenotypes for dissecting genetic elements of pathogenicity.
Main Methods:
- In vitro culture of Clonal Borrelia burgdorferi N40 (cN40) through serial passaging (75 and 120 times).
- Infection studies in mouse models to assess infectivity and disease manifestation.
- Molecular analysis to identify genetic differences, including the presence or absence of genes on linear plasmids.
Main Results:
- Clonal Borrelia burgdorferi N40 (cN40) passaged 75 times (N40-75) infected mice but did not cause disease.
- Further passaging to N40-120 resulted in a complete loss of infectivity.
- The N40-120 strain lacked genes encoded on linear plasmids 38 and 28-1, among other genetic alterations.
Conclusions:
- Extensive in vitro passaging significantly attenuates Borrelia burgdorferi infectivity and pathogenicity.
- The loss of specific genes, particularly those on linear plasmids, is associated with reduced virulence.
- Distinct phenotypes of passaged B. burgdorferi strains provide a valuable model for studying the genetic determinants of pathogenicity and infectivity.