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Hitchhiker’s Guide to Borrelia burgdorferi – an excellent backgrounder on Lyme disease for biologists

By the end of the review, you may discover that you have more in common with the bemused Arthur Dent than you might have expected.

Figure illustration of transmission and life cycle of ticks, cheekily placed on top of a photo of the Milky Way galaxy.

This mini-review, written in a very engaging manner by Bourgeois and Hu (2024), highlights important points that might not be obvious to people just beginning their involvement with the biology of Lyme disease.

Unique attributes

Cycling between mammals and ticks, Borrelia burgdorferi changes its coat both to take advantage of the immune system in establishing infection and to avoid the immune system of the host it’s trying to invade. This complexity is well demonstrated by the failed vaccine candidate, based on the decorin binding protein A, which provided protection against needle inoculations but not protection against feeding by infected ticks. 

The genome of Borrelia burgdorferi is equally quirky: one linear chromosome and approximately 21 plasmids, the exact number differing among strains. Unlike E. coli, B. burgdorferi has abundant genes expressing lipoproteins and a genome lacking expected metabolic pathways. Instead of producing many nutrients, it uses transporter proteins to capture nutrients from its host. The ultimate manipulator, B. burgdorferi has plasmids that can encode a prophage, produced in the tick and providing a possible route for horizontal gene transfer. 

B. burgdorferi is present in very low numbers in host tissues making this a difficult organism to study, especially in mammals. However, intravital imaging of fluorescently labeled bacteria has been a useful tool with luciferase-based and digital-droplet PCR now showing their worth. 

If your eyes are starting to glaze over, skip to the section on selected insights from the use of B. burgdorferi models of infections. You’re sure to find something to catch your imagination. For example, did you know that B. burgdorferi lacks traditional virulence factors? It’s co-opted proteins in tick saliva to do its bidding. After 10 days or so, B. burgdorferi enters stealth mode and the story gets darker. 

By the end of the review, you may discover that you have more in common with the bemused Arthur Dent than you might have expected. 

Citation

Bourgeois JS, Hu LT. 0. Hitchhiker’s Guide to Borrelia burgdorferi. J Bacteriol 0:e00116-24. https://doi.org/10.1128/jb.00116-24

Figure 2

Transmission and life cycle illustration.
Fig 2 Understanding B. burgdorferi spread in nature. B. burgdorferi vectors, Ixodes ticks, take three blood meals throughout their lifetimes over the course of 2 years: once as larvae, once as nymphs, and once as adults. In spring, the nymphal I. scapularis blood meal enables B. burgdorferi to spread into reservoir hosts, typically small mammals or birds. Later in the year, larvae feed on these colonized reservoirs, which results in the acquisition of the spirochete by new ticks. Finally, in the fall adult Ixodes feed on larger vertebrates. Notably, the infection status of the tick has very little impact on the spread of B. burgdorferi in the adult stage, as the hosts that adult I. scapularis feed on are typically non-permissive or dead-end hosts for B. burgdorferi. Instead, this stage is important for the continued propagation of the tick vector. Red animals represent B. burgdorferi colonization, and the red arrows represent the direction of B. burgdorferi spread at each tick life stage. The adult tick is represented as both gray and red to represent that both colonized and B. burgdorferi-free adult ticks contribute to I. scapularis reproduction.

Abstract

In the nearly 50 years since the discovery of Lyme disease, Borrelia burgdorferi has emerged as an unlikely workhorse of microbiology. Interest in studying host-pathogen interactions fueled significant progress in making the fastidious microbe approachable in laboratory settings, including the development of culture methods, animal models, and genetic tools. By developing these systems, insight has been gained into how the microbe is able to survive its enzootic cycle and cause human disease. Here, we discuss the discovery of B. burgdorferi and its development as a model organism before diving into the critical lessons we have learned about B. burgdorferi biology at pivotal stages of its lifecycle: gene expression changes during the tick blood meal, colonization of a new vertebrate host, and developing a long-lasting infection in that vertebrate until a new tick feeds. Our goal is to highlight the advancements that have facilitated B. burgdorferi research and identify gaps in our current understanding of the microbe

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