A groundbreaking study shows how Borrelia burgdorferi slips through the skin’s tiny vessels to spread Lyme disease.
A new study published in Nature Communications (October 2025) has revealed, for the first time in microscopic detail, exactly how Borrelia burgdorferi—the bacteria that causes Lyme disease—enters the body and begins its systemic spread, providing vital insights for Lyme disease research.
Researchers at the Czech Academy of Sciences used AI-assisted 3D electron microscopy to observe the earliest moments of infection at the tick bite site. Their images show that Borrelia does not enter the bloodstream randomly. Instead, it targets specific weak spots in the skin’s network of blood and lymph vessels, using them as strategic gateways to invade the body.
A High-Tech Look at the Lyme Bacteria in Action
Until now, most studies of Lyme disease infection relied on lab-grown cell models that couldn’t fully replicate how human tissues behave. This new research used an advanced imaging technique called serial block-face scanning electron microscopy (SBF-SEM) to create 3D, nanoscale views of the skin right after a tick bite.
These findings have significant implications for Lyme disease research, shedding light on how the bacteria initially invades human tissue and highlighting the importance of ongoing Lyme disease research in understanding and combating the infection.
By combining powerful imaging with AI segmentation tools, the team captured Borrelia interacting with blood and lymphatic capillaries—the smallest vessels in the skin—down to individual cell layers. The result is the most detailed structural map ever made of Lyme bacteria moving through living tissue.
Two Main Routes Into the Body
The researchers observed Borrelia burgdorferi using two main invasion strategies:
1. Transcellular Route – Tunneling Through Cells
The bacteria penetrate directly through the cells that line lymphatic vessels, known as endothelial cells. Using its flexible, corkscrew-shaped body, Borrelia creates tiny membrane tunnels that gradually wrap around the bacterium. It moves in segment by segment—almost like a zipper closing behind it—until it’s fully inside the vessel.
2. Paracellular Route – Squeezing Between Cells
In other cases, the bacteria slip between neighboring endothelial cells at points where cell junctions are naturally looser. Once inside the vessel’s inner space, called the lumen, Borrelia can move freely through the lymphatic system, which drains fluid and connects to the immune network.
This dual strategy allows Borrelia to bypass many of the body’s physical barriers. The lymphatic vessels, which are thinner and less fortified than blood vessels, appear to be its preferred “on-ramp” for early dissemination.
Pericytes: The Hidden Gatekeepers Lyme Exploits
One of the most surprising findings was that Borrelia specifically targets pericytes—specialized support cells wrapped around blood vessels that help maintain vessel stability and control what passes in and out.
Under normal conditions, pericytes strengthen the vessel wall. But by attaching to them, Borrelia appears to exploit their softer structure. The bacteria often position themselves between pericytes and the endothelial layer, where the vessel wall is weakest.
These interactions suggest that Lyme bacteria may compromise the mechanical stability of blood vessels to prepare for eventual spread into the bloodstream. It’s a stealth strategy that allows invasion without destroying tissue or triggering a strong inflammatory alarm.
Four Movement Styles That Drive Invasion
The study also explained how the Lyme bacteria’s movement patterns—called motility states—help them breach tissue barriers. Inside the skin, Borrelia alternates between four motion modes:
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Passive: not moving.
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Wriggling: twisting back and forth in place.
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Lunging: bending while one end is anchored.
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Translocating: propelling forward in a straight line.
These motions aren’t random. The wriggling and lunging states appear to physically deform host cell membranes, helping the bacteria open entry points. The translocating state allows them to push deeper into tissue and align along vessel walls, while stationary phases let them “wait out” immune attacks unnoticed.
The Role of Collagen and the Extracellular Matrix
Once transmitted through a tick bite, Borrelia first moves through the extracellular matrix (ECM)—the dense network of collagen and connective tissue beneath the skin.
The study found that Borrelia often aligns itself with collagen fibers instead of breaking them down. This means it uses the body’s existing tissue architecture as a natural pathway. Unlike many invasive bacteria, Borrelia doesn’t secrete large amounts of tissue-dissolving enzymes early on, which helps it avoid detection by the immune system.
This “low-damage” approach supports a broader evolutionary strategy: move stealthily, spread efficiently, and trigger minimal immune alarm.
The Immune System Fights Back — But Not Fast Enough
Even within a few hours of infection, the immune system begins to respond. Researchers observed:
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Mast cells releasing granules that signal inflammation.
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Neutrophils migrating toward the infection site.
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Neutrophils engulfing spirochetes (the spiral-shaped bacteria) inside phagosomes.
Despite this quick response, Borrelia manages to survive and spread. The study showed minimal tissue damage at this early stage, suggesting that Borrelia’s stealthy invasion helps it avoid full immune activation—giving it a head start before symptoms like erythema migrans (the rash) appear.
A New Understanding of How Lyme Spreads
The researchers concluded that early in infection:
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Borrelia primarily enters lymphatic vessels, not blood vessels.
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The basement membrane (BM) under blood vessels is a tougher barrier than previously thought.
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Once in the lymphatic system, Borrelia can travel to distant tissues and organs, explaining how Lyme disease becomes systemic so quickly.
These discoveries reshape our understanding of Lyme disease’s earliest phase. By showing where and how Borrelia crosses into the body’s circulation, scientists can now look for new ways to block vascular entry and prevent long-term infection.
Study Summary
- Title: Targeted Volume Imaging Reveals Early Vascular Interactions of Lyme Disease Pathogen in Skin
- Authors: Martin Strnad, Jiří Týč, František Kitzberger, Jana Kopecká, Ryan O. M. Rego, Marie Vancová
- Institution: Institute of Parasitology, Biology Centre, Czech Academy of Sciences
- Published: Nature Communications (October 2025)
- DOI: 10.1038/s41467-025-64326-w
Why This Matters for Patients and Advocates
This study gives validation to what many patients already experience: Lyme disease spreads quickly and systemically, often before symptoms are obvious.
It also underscores the importance of early diagnosis and prompt treatment—since the bacteria can enter the body’s circulatory systems within hours of a tick bite.
For the research community, it highlights new therapeutic targets:
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Strengthening vascular barriers.
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Blocking pericyte or fibronectin interactions.
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Targeting Borrelia’s motility mechanisms to prevent dissemination.
These findings deepen scientific understanding of Lyme disease and move us closer to prevention strategies that can stop infection before it spreads throughout the body.
