Antigenic Variation in the Lyme Spirochete: Insights into Recombinational Switching with a Suggested Role for Error-Prone Repair

Publication date: 29 May 2018
Source:Cell Reports, Volume 23, Issue 9
Author(s): Theodore B. Verhey, Mildred Castellanos, George Chaconas
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.

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Teaser

The Lyme disease spirochete is a master of disguise and escapes the host immune system by continually changing a major surface lipoprotein, VlsE. Using next- generation sequencing and by designing a computer algorithm, Verhey et al. reveal insights into the mechanism of the recombination reaction that drives antigenic variation.


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