Lyme Disease Pathogenesis and Host Interactions

Lyme disease arises from infection by the spirochete Borrelia burgdorferi transmitted via Ixodes ticks. The pathogen adapts to divergent host environments through dynamic regulation of gene expression, including alternative sigma factor cascades that orchestrate surface protein shifts essential for tick colonisation, mammalian invasion and immune evasion. Dissemination to distal tissues relies on motility and adhesin-mediated vascular interactions, allowing extravasation into joints, heart and nervous system. Host inflammatory responses drive the majority of clinical manifestations, from erythema migrans to neuroborreliosis and arthritis. RNA regulators, lipid exchanges and complement-evasion proteins further modulate host–pathogen interplay, providing new therapeutic targets worldwide.

Research from Nature Portfolio

Recent studies have applied high-resolution RNA sequencing to the Borrelia transcriptome, uncovering an abundance of regulatory RNAs and complex operon structures. Mapping of RNA 3′ ends showed that 63% lie within or upstream of coding regions, indicative of premature termination events that fine-tune expression of infection-relevant genes. Both intrinsic and Rho-dependent termination sites were characterised, and spermidine was found to influence mRNA truncation globally. These insights reveal a sophisticated layer of post-transcriptional control in the pathogen’s adaptive cycle, pointing to novel intervention strategies aimed at disrupting essential RNA regulators.

Lyme Disease Pathogenesis and Host Interactions publication trend

The graph below shows the total number of articles in lyme disease pathogenesis and host interactions across all publications each year (not limited to Nature Index journals).

Technical terms

Spirochete: A helical, motile bacterium with axial flagella enabling tissue penetration and dissemination.

Enzootic cycle: The natural transmission cycle of a pathogen between vector and reservoir host.

Sigma factor: A protein subunit of RNA polymerase that directs initiation at specific promoters.

Rho-dependent termination: A mechanism whereby the Rho protein binds nascent RNA and induces transcription termination.

Extravasation: The process of a pathogen crossing the endothelial barrier from the bloodstream into surrounding tissues.

References

1. Extensive diversity in RNA termination and regulation revealed by transcriptome mapping for the Lyme pathogen Borrelia burgdorferi. Nature Communications (2023).
2. A Fur family protein BosR is a novel RNA-binding protein that controls rpoS RNA stability in the Lyme disease pathogen. Nucleic Acids Research (2024).
3. Extravasation of Borrelia burgdorferi Across the Blood–Brain Barrier is an Extremely Rare Event. Advanced Science (2025).
4. BosR and PlzA reciprocally regulate RpoS function to sustain Borrelia burgdorferi in ticks and mammals. Journal of Clinical Investigation (2023).
5. Borrelia burgdorferi Keeps Moving and Carries on: A Review of Borrelial Dissemination and Invasion. Frontiers in Immunology (2017).
6. Lyme Disease Pathogenesis.. Current Issues in Molecular Biology (2020).
7. Microbes Bind Complement Inhibitor Factor H via a Common Site. PLOS Pathogens (2013).
8. Lipid Exchange between Borrelia burgdorferi and Host Cells. PLOS Pathogens (2013).