Antigenic Variation in the Lyme Spirochete: Insights into Recombinational Switching with a Suggested Role for Error-Prone Repair
The Lyme disease spirochete, Borrelia burgdorferi, uses antigenic variation as a strategy to evade the host’s acquired immune response. New variants of surface-localized VlsE are generated efficiently by unidirectional recombination from 15 unexpressed vls cassettes into the vlsE locus. Using algori...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-05-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718307174 |
| _version_ | 1818694663890010112 |
|---|---|
| author | Theodore B. Verhey Mildred Castellanos George Chaconas |
| author_facet | Theodore B. Verhey Mildred Castellanos George Chaconas |
| author_sort | Theodore B. Verhey |
| collection | DOAJ |
| description | The Lyme disease spirochete, Borrelia burgdorferi, uses antigenic variation as a strategy to evade the host’s acquired immune response. New variants of surface-localized VlsE are generated efficiently by unidirectional recombination from 15 unexpressed vls cassettes into the vlsE locus. Using algorithms to analyze switching from vlsE sequencing data, we characterize a population of over 45,000 inferred recombination events generated during mouse infection. We present evidence for clustering of these recombination events within the population and along the vlsE gene, a role for the direct repeats flanking the variable region in vlsE, and the importance of sequence homology in determining the location of recombination, despite RecA’s dispensability. Finally, we report that non-templated sequence variation is strongly associated with recombinational switching and occurs predominantly at the 5′ end of conversion tracts. This likely results from an error-prone repair mechanism operational during recombinational switching that elevates the mutation rate > 5,000-fold in switched regions. |
| first_indexed | 2024-12-17T13:33:10Z |
| format | Article |
| id | doaj.art-c18ba89b841a4f3e89dabf8f693f0d07 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-17T13:33:10Z |
| publishDate | 2018-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-c18ba89b841a4f3e89dabf8f693f0d072022-12-21T21:46:31ZengElsevierCell Reports2211-12472018-05-012392595260510.1016/j.celrep.2018.04.117Antigenic Variation in the Lyme Spirochete: Insights into Recombinational Switching with a Suggested Role for Error-Prone RepairTheodore B. Verhey0Mildred Castellanos1George Chaconas2Department of Biochemistry and Molecular Biology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, CanadaDepartment of Biochemistry and Molecular Biology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, CanadaDepartment of Biochemistry and Molecular Biology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, CanadaThe Lyme disease spirochete, Borrelia burgdorferi, uses antigenic variation as a strategy to evade the host’s acquired immune response. New variants of surface-localized VlsE are generated efficiently by unidirectional recombination from 15 unexpressed vls cassettes into the vlsE locus. Using algorithms to analyze switching from vlsE sequencing data, we characterize a population of over 45,000 inferred recombination events generated during mouse infection. We present evidence for clustering of these recombination events within the population and along the vlsE gene, a role for the direct repeats flanking the variable region in vlsE, and the importance of sequence homology in determining the location of recombination, despite RecA’s dispensability. Finally, we report that non-templated sequence variation is strongly associated with recombinational switching and occurs predominantly at the 5′ end of conversion tracts. This likely results from an error-prone repair mechanism operational during recombinational switching that elevates the mutation rate > 5,000-fold in switched regions.http://www.sciencedirect.com/science/article/pii/S2211124718307174antigenic variationBorrelia burgdorferi, Lyme diseasevlsEsegmental gene conversionexpression locussilent cassetteserror-prone repair |
| spellingShingle | Theodore B. Verhey Mildred Castellanos George Chaconas Antigenic Variation in the Lyme Spirochete: Insights into Recombinational Switching with a Suggested Role for Error-Prone Repair Cell Reports antigenic variation Borrelia burgdorferi, Lyme disease vlsE segmental gene conversion expression locus silent cassettes error-prone repair |
| title | Antigenic Variation in the Lyme Spirochete: Insights into Recombinational Switching with a Suggested Role for Error-Prone Repair |
| title_full | Antigenic Variation in the Lyme Spirochete: Insights into Recombinational Switching with a Suggested Role for Error-Prone Repair |
| title_fullStr | Antigenic Variation in the Lyme Spirochete: Insights into Recombinational Switching with a Suggested Role for Error-Prone Repair |
| title_full_unstemmed | Antigenic Variation in the Lyme Spirochete: Insights into Recombinational Switching with a Suggested Role for Error-Prone Repair |
| title_short | Antigenic Variation in the Lyme Spirochete: Insights into Recombinational Switching with a Suggested Role for Error-Prone Repair |
| title_sort | antigenic variation in the lyme spirochete insights into recombinational switching with a suggested role for error prone repair |
| topic | antigenic variation Borrelia burgdorferi, Lyme disease vlsE segmental gene conversion expression locus silent cassettes error-prone repair |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718307174 |
| work_keys_str_mv | AT theodorebverhey antigenicvariationinthelymespirocheteinsightsintorecombinationalswitchingwithasuggestedroleforerrorpronerepair AT mildredcastellanos antigenicvariationinthelymespirocheteinsightsintorecombinationalswitchingwithasuggestedroleforerrorpronerepair AT georgechaconas antigenicvariationinthelymespirocheteinsightsintorecombinationalswitchingwithasuggestedroleforerrorpronerepair |