Antigenic variation in the Lyme spirochete: detailed functional assessment of recombinational switching at vlsE in the JD1 strain of Borrelia burgdorferi

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dc.contributor.authorVerhey, Theodore B
dc.contributor.authorCastellanos, Mildred
dc.contributor.authorChaconas, George
dc.date.accessioned2019-05-28T19:04:33Z
dc.date.available2019-05-28T19:04:33Z
dc.date.issued2019-01
dc.description.abstractBorrelia burgdorferi is a causative agent of Lyme disease and establishes long-term infection in mammalian hosts. Persistence is promoted by the VlsE antigenic variation system, which generates combinatorial diversity of VlsE through unidirectional, segmental gene conversion from an array of silent cassettes. Here we explore the variants generated by the vls system of strain JD1, which has divergent sequence and structural elements from the type strain B31, the only B. burgdorferi strain in which recombinational switching at vlsE has been studied in detail. We first completed the sequencing of the vls region in JD1, uncovering a previously unreported 114 bp inverted repeat sequence upstream of vlsE. A five-week infection of WT and SCID mice was used for PacBio long read sequencing along with our recently developed VAST pipeline to analyze recombinational switching at vlsE from 40,000 sequences comprising 226,000 inferred recombination events. We show that antigenic variation in B31 and JD1 is highly similar, despite the lack of 17 bp direct repeats in JD1, a somewhat different arrangement of the silent cassettes, divergent inverted repeat sequences and general divergence in the vls sequences. We also present data that strongly suggest that dimerization is required for in vivo functionality of VlsE.en_US
dc.description.grantingagencyCanadian Institutes of Health Research - Foundation Schemeen_US
dc.identifier.citationVerhey, T. B., Castellanos, M. and Chaconas, G. (2019), Antigenic variation in the Lyme spirochete: detailed functional assessment of recombinational switching at vlsE in the JD1 strain of Borrelia burgdorferi. Mol Microbiol, 111: 750-763. doi:10.1111/mmi.14189en_US
dc.identifier.doihttp://dx.doi.org/10.1111/mmi.14189en_US
dc.identifier.grantnumberMOP-53086en_US
dc.identifier.grantnumberPJT-153336
dc.identifier.urihttp://hdl.handle.net/1880/110440
dc.language.isoengen_US
dc.publisherWileyen_US
dc.publisher.departmentBiochemistry & Molecular Biologyen_US
dc.publisher.departmentMicrobiology, Immunology & Infectious Diseasesen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.hasversionPost-printen_US
dc.publisher.institutionUniversity of Calgaryen_US
dc.publisher.policyhttps://authorservices.wiley.com/author-resources/Journal-Authors/licensing/self-archiving.htmlen_US
dc.titleAntigenic variation in the Lyme spirochete: detailed functional assessment of recombinational switching at vlsE in the JD1 strain of Borrelia burgdorferien_US
dc.typejournal articleen_US
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