Comment; Technical review article that delves into the immunology, how the VIsE locus/antigenic group allows the tick vector to remain assymptomatic while only mammalian hosts are harmed–a great way to transmit a disease!
Christa Winslow https://orcid.org/0000-0001-8976-91041, Jenifer Coburn1,2Author details
Abstract
This review highlights some of the highest-profile developments and advancements in the research on Borrelia burgdorferi, the Lyme disease spirochete, that have emerged in the last two years. Particular emphasis is placed on the controversy surrounding genus nomenclature, antigenic variation at the vlsE locus, genes involved in infectivity and virulence, membrane characteristics of B. burgdorferi, and developments in experimental approaches.
Introduction
Borrelia burgdorferi is an intriguing and unique bacterium. It is most notorious for being the primary causative agent of Lyme disease in North America1. With more than 42,000 probable and confirmed cases reported to the Centers for Disease Control and Prevention (CDC) in 2017 and other estimates in the range of 300,000 cases annually in the US, Lyme disease is the most common arthropod-borne disease in North America and Europe2,3 (CDC, https://www.cdc.gov/lyme/datasurveillance/index.html). Case numbers have increased over the past several years and continue to be a growing concern as the range of the tick vector, Ixodes scapularis in particular, expands in North America4 (CDC, https://www.cdc.gov/lyme/datasurveillance/index.html). Although antibiotic regimens are available and effective for treating the early stages of infection, Lyme disease often progresses without diagnosis5. Serious long-term effects include arthritis, carditis, and neuroborreliosis5,6. Consequently, much research has focused on the development of a vaccine to administer to humans in endemic regions such as the Northeast and upper Midwest of the US7.
B. burgdorferi is a motile, Gram-negative, pathogenic spirochete with a highly segmented genome composed of a linear chromosome and about 20 linear and circular genomic plasmids1,8. It exists in an enzootic life cycle alternating between specific Ixodes ticks and vertebrates9. Humans can become incidental hosts through the bite of an infected tick9. Whereas some Borrelia species, including B. burgdorferi, cause Lyme disease, other species cause relapsing fever, which is characterized by recurring episodes of fever and illness correlated with the bacterial burden in the bloodstream10.
The focus of this article is to briefly highlight some of the major developments and advancements in understanding B. burgdorferi published within the last two years. As such, the content of this review is inherently selected on the basis of the authors’ interests and perspectives. Nevertheless, this article provides a summary of some of the most significant recent developments regarding genus nomenclature, antigenic variation at the vls locus, genes involved in infectivity and virulence, membrane chemistry, and advancements in laboratory techniques.
Conclusions
Although the word limit of this review requires that we not include the vast majority of recent publications, it is hoped that some major themes, advancements, and future directions are clear. Controversy surrounding genus nomenclature persists for now but hopefully will be resolved so energy can again be directed toward the biology of the organisms and the diseases they cause. Further research into the antigenic variation system encoded at the vls system is now enabled by PacBio long-read sequencing and the VAST program to track genetic changes in B. burgdorferi. The mechanisms behind this unique segmental gene conversion system, and therefore the antigenic variation system that allows B. burgdorferi to maintain infections, deserve more study. We look forward to seeing how this area of research unfolds and its implications for the biology of the Lyme disease agents. Similarly, we anticipate the identification and investigation of more genes essential to B. burgdorferi infectivity and virulence. In addition to increasing our understanding of B. burgdorferi biology, these studies may direct investigation of future vaccine targets. We also sought to highlight the protein and lipid characteristics of the B. burgdorferi membranes. In light of its existence as an extracellular pathogen, these characteristics and dynamic changes are significant for interactions of B. burgdorferi with its environment, be it tick or vertebrate. By extension, general understanding of the physiology of B. burgdorferi, obtained through the applications of newly pioneered laboratory techniques, will uncover the secrets of this fascinating spirochete.
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