Background
Lyme disease is the most widespread tick-borne illness in North America and Europe. Every year, approximately 476,000 people in the United States develop Lyme disease. Borrelia burgdorferi sensu stricto, or B. burgdorferi, is the principal causal agent. Following a bite by an infected black-legged tick (Ixodes scapularis) or western black-legged tick (Ixodes pacificus), B. burgdorferi spreads throughout the circulation to infect various tissues, such as the joints, brain, and heart, resulting in a chronic infection. Lyme disease presents with a variety of symptoms. Early localized infection may result in flu-like symptoms and the distinctive erythema migrans rash. As the infection develops, neurological symptoms such as facial palsy, neuritis, meningitis, and Lyme carditis can appear within months. In late-stage Lyme disease, chronic symptoms such as arthritis, peripheral neuropathy, severe fatigue, and other long-term complications can occur.
Antibiotic treatment is the most effective way to combat Lyme disease. Three kinds of antibiotics—tetracyclines, β-lactam antibiotics, and, to a lesser extent, macrolides—are effective against B. burgdorferi. However, chronic Lyme disease symptoms can last for years even after receiving antibiotic treatment (post-treatment Lyme disease syndrome, or PTLDS), which is why vaccination against Lyme disease is crucial. The surface of Borrelia spirochetes is decorated with various surface proteins, which are potential targets for vaccine development and have been a focus of research. Researchers created two vaccines based on the surface protein OspA in the 1990s, but they were withdrawn due to a lack of licensure and serious adverse effects. Subsequently, efforts have shifted toward other surface proteins, such as the Variable major protein-like sequence Expressed (VlsE).
VlsE is a highly variable guard protein that continuously modifies its sequence through segmental gene conversion events, allowing B. burgdorferi to stay ahead of the immune response and evade the host's immune system. Besides its crucial role in immune evasion, recent studies suggest that VlsE may have other potential functions, such as adhesive properties similar to another surface protein, OspC. Clinically, recombinant VlsE can be used for the diagnosis and further study of Lyme disease. It can serve as an antigen in ELISA and immunoblot assays, aid in researching the pathogenesis of Lyme disease, and assist in developing new vaccines and drugs. Additionally, it can be used to evaluate treatment efficacy and disease progression, helping to formulate effective treatment plans.
Alternative Names
Borrelia burgdorferi VlsE
VlsE Lyme disease
Recombinant vlse
Variable major protein-like sequence Expressed
References
VlsE, the nexus for antigenic variation of the Lyme disease spirochete, also mediates early bacterial attachment to the host microvasculature under shear force
PLoS Pathogens
Authors: Tan, X. Lin, YP. Pereira, MJ. Castellanos, M. Hahn, BL. Anderson, P. Coburn, J. Leong, JM. Chaconas G.
Abstract
Hematogenous dissemination is a critical step in the evolution of local infection to systemic disease. The Lyme disease (LD) spirochete, which efficiently disseminates to multiple tissues, has provided a model for this process, in particular for the key early event of pathogen adhesion to the host vasculature. This occurs under shear force mediated by interactions between bacterial adhesins and mammalian cell-surface proteins or extracellular matrix (ECM). Using real-time intravital imaging of the Lyme spirochete in living mice, we previously identified BBK32 as the first LD spirochetal adhesin demonstrated to mediate early vascular adhesion in a living mouse; however, deletion of bbk32 resulted in loss of only about half of the early interactions, suggesting the existence of at least one other adhesin (adhesin-X) that promotes early vascular interactions. VlsE, a surface lipoprotein, was identified long ago by its capacity to undergo rapid antigenic variation, is upregulated in the mammalian host and required for persistent infection in immunocompetent mice. In immunodeficient mice, VlsE shares functional overlap with OspC, a multi-functional protein that displays dermatan sulfate-binding activity and is required for joint invasion and colonization. In this research, using biochemical and genetic approaches as well as intravital imaging, we have identified VlsE as adhesin-X; it is a dermatan sulfate (DS) adhesin that efficiently promotes transient adhesion to the microvasculature under shear force via its DS binding pocket. Intravenous inoculation of mice with a low-passage infectious B.?burgdorferi strain lacking both bbk32 and vlsE almost completely eliminated transient microvascular interactions. Comparative analysis of binding parameters of VlsE, BBK32 and OspC provides a possible explanation why these three DS adhesins display different functionality in terms of their ability to promote early microvascular interactions.
Changing of the guard: How the Lyme disease spirochete subverts the host immune response
Journal of Biological Chemistry
Authors: Chaconas, G. Castellanos, M. B.Verhey, T.
Abstract
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 nearly 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.
COA
Publication 
![The purity of Recombinant B.burgdorferi OspC protein [His] >95%, determined by SDS-PAGE](https://resource.creative-diagnostics.com/diagnostics/productimages-1/DAGA-2006-1.jpg)
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