Changing of the guard: How the Lyme disease spirochete subverts the host immune response

TitleChanging of the guard: How the Lyme disease spirochete subverts the host immune response
Publication TypeJournal Article
Year of Publication2019
AuthorsChaconas G, Castellanos M, Verhey TB
JournalJ Biol Chem
Date Published11/2019
Keywordsantigenic variation, bacterial genetics, bacterial pathogenesis, borrelia, DNA mismatch repair, DNA recombination, G-quadruplex, genetic polymorphism, infectious disease, Lyme disease

Lyme disease, also known as Lyme borreliosis, is the most common tick-transmitted disease in the Northern Hemisphere. The disease is caused by the bacterial spirochete Borrelia burgdorferi and other related Borrelia species. One of the many fascinating features of this unique pathogen is an elaborate system for antigenic variation whereby the sequence of the surface-bound lipoprotein VlsE is continually modified through segmental gene conversion events. This perpetual changing of the guard allows the pathogen to remain one step ahead of the acquired immune response, enabling persistent infection. Accordingly, the vls locus is the most evolutionarily diverse genetic element in Lyme disease-causing borreliae. Small stretches of information are transferred from a series of silent cassettes in the vls locus to generate an expressed mosaic vlsE gene version that contains genetic information from several different silent cassettes, resulting in ~1040 possible vlsE sequences. Yet, despite its extreme evolutionary flexibility, the locus has rigidly conserved structural features. These include a telomeric location of the vlsE gene, an inverse orientation of vlsE and the silent cassettes, the presence of near-perfect inverted repeats of ~100 bp near the 5' end of vlsE, and an exceedingly high concentration of G runs in vlsE and the silent cassettes. We discuss the possible roles of these evolutionarily conserved features, highlight recent findings from several studies that have used next-generation DNA sequencing to unravel the switching process, and review advances in the development of a mini-vls system for genetic manipulation of the locus.