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Cultivation Methods of Spirochetes from Borrelia burgdorferi Sensu Lato Complex and Relapsing Fever Borrelia
Published on: November 25, 2022
Antigenic variation is caused by long plasmid segment conversion in a hard tick-borne relapsing fever Borrelia
Tomohi Takeuchi1, Yasuhiro Gotoh2, Tetsuya Hayashi3
1Department of Veterinary Medicine, Joint Graduate School of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.
Abstract:
Borrelia miyamotoi is a hard tick-borne spirochete genetically related to relapsing fever Borrelia and the etiological agent of an emerging infectious disease in humans. Like relapsing fever Borrelia, B. miyamotoi carries clusters of gene cassettes encoding variable major proteins (Vmps) on multiple linear plasmids and shows antigenic variation in mammalian hosts by switching the expression vmp gene cassette. However, it remains unknown how the switch occurs in B. miyamotoi. Here we determined the whole genome sequences of Japanese B. miyamotoi strains to identify the repertoire and arrangement of vmp gene cassettes on five linear plasmids, and based on this information, analyzed B. miyamotoi clones reisolated from experimentally infected mice. Our analyses revealed that the switch occurred by replacing the expression cassette and its downstream silent cassettes with the long segment from archival plasmid. As the result of this long segment conversion, the first cassette became the expression cassette. Notably, this phenomenon was not due to single gene conversion but the replacement of a long (up to 16 kb or more) plasmid segment. We also show that while bacterial elimination depended on the presence of specific antibodies, the segment conversion was detected at five days post-infection, earlier than antibody production in mice, and even in severe combined immunodeficient mice. These results provide novel insights into the mechanisms that Borrelia evolved to survive and persist in mammalian hosts.
Insights
Borrelia miyamotoi evades the immune system by replacing gene cassettes on its plasmids. This process involves replacing a long DNA segment, not just a single gene, enabling survival in hosts.
Area of Science:
- Microbiology
- Genetics
- Immunology
Background:
- Borrelia miyamotoi is a tick-borne spirochete causing emerging infectious diseases.
- It exhibits antigenic variation via variable major protein (Vmp) gene switching, similar to relapsing fever Borrelia.
- The mechanism of Vmp gene switching in B. miyamotoi was previously unknown.
Purpose of the Study:
- To elucidate the mechanism of antigenic variation in Borrelia miyamotoi.
- To identify the repertoire and arrangement of Vmp gene cassettes on B. miyamotoi linear plasmids.
- To analyze Vmp gene switching in B. miyamotoi reisolated from infected mice.
Main Methods:
- Whole genome sequencing of Japanese B. miyamotoi strains.
- Analysis of Vmp gene cassette arrangement on five linear plasmids.
- Characterization of B. miyamotoi clones from experimentally infected mice.
Main Results:
- The Vmp gene switch in B. miyamotoi involves replacing the expression cassette and downstream silent cassettes with a long segment from an archival plasmid.
- This long segment conversion (up to 16kb or more) results in the first cassette becoming the new expression cassette.
- Segment conversion occurs early in infection (5 days post-infection), preceding antibody production, and is observed even in immunodeficient mice.
Conclusions:
- Borrelia miyamotoi utilizes a novel mechanism of large-scale DNA segment replacement for antigenic variation.
- This mechanism allows for immune evasion and persistence in mammalian hosts, independent of early host antibody response.
- Findings provide crucial insights into bacterial survival strategies in hosts.
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