Borrelia Persister Cells: Why Lyme Disease Can Persist

Borrelia can survive antibiotic treatment.
Some bacteria enter a dormant “persister” state.
This may help explain persistent Lyme symptoms.

Persister cells are a form of bacteria that can survive antibiotic treatment without being genetically resistant—and may help explain why Lyme disease can persist.

This phenomenon is widely accepted in microbiology, although its role in human Lyme disease remains an area of ongoing research.

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What Are Persister Cells?

Persister cells are bacteria that enter a temporary, dormant state.

Because most antibiotics target actively dividing bacteria, these dormant cells can survive treatment.

This allows bacteria to persist without developing traditional antibiotic resistance.

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Evidence of Borrelia Persistence

“Though its applicability to B. burgdorferi has been controversial, persistence is a widely-accepted phenomenon in microbiology,” according to Cabello.

There are numerous reports of antimicrobial treatment unable to completely eliminate B. burgdorferi from tissues in experimentally infected rodents and nonhuman primates.

These findings suggest that Borrelia may survive despite antibiotic exposure under certain conditions.

While these findings are compelling, their direct relevance to human Lyme disease continues to be studied.

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How Borrelia Adapts and Survives

The ability of spirochetes to survive in a tick, then in an animal host, and back to the tick may explain the development of persister cells.

These transitions require metabolic and morphologic changes that can increase tolerance to environmental stress and antimicrobial exposure.

Such adaptations may allow Borrelia to tolerate otherwise lethal conditions.

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Phenotypic Changes in Borrelia

Spirochetes can become tolerant to antimicrobials through phenotypic changes—adaptations that occur without genetic mutation.

• In ticks, Borrelia expresses outer surface protein A (OspA)
• In vertebrates, it switches to outer surface protein C (OspC)

These changes help Borrelia survive in very different environments.

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Antibiotic Tolerance in Laboratory Studies

“Stationary phase B. burgdorferi cells in culture can become phenotypically tolerant to antimicrobials such as ceftriaxone, doxycycline, and amoxicillin,” according to Cabello.

Researchers have identified:

• Antimicrobial-tolerant Borrelia in suspension cultures
• Biofilm-like communities
• Quiescent round-body forms under stress

These forms may act as reservoirs for persister cells.

Persistence is considered a phenotypic phenomenon and does not necessarily imply antibiotic resistance.

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Where Borrelia May Persist

Borrelia may survive in protected areas of the body, sometimes referred to as “refugia.”

“Borrelia burgdorferi can colonize and persist in multiple tissue sites despite vigorous host immune responses,” writes Cabello.

These areas may include:

• Collagen-rich tissues
• Avascular regions with limited immune access

In these environments, Borrelia may persist even when not actively replicating.

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Why Persister Cells Matter Clinically

This may help explain why some patients continue to experience symptoms despite standard antibiotic treatment.

Persistence does not necessarily mean antibiotic resistance, but it may contribute to ongoing disease activity.

The clinical significance of persister cells in Lyme disease remains an area of active investigation.

For related clinical context, see Post-Treatment Lyme Disease Syndrome (PTLDS).

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Clinical Takeaway

Persister cells are a recognized phenomenon in microbiology and may play a role in Lyme disease persistence.

Understanding how Borrelia adapts and survives is important for interpreting persistent symptoms and guiding care.

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Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.

Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention