Can Lyme Disease Remain Dormant? What Borrelia Persister Research Shows

Can Lyme disease symptoms appear years after infection?
Laboratory studies have identified Borrelia persister cells
Researchers continue to investigate what these findings mean for patients

Can Lyme disease symptoms appear months or years after a tick bite? This question often leads patients to wonder whether the bacteria can remain dormant. Laboratory studies have shown that Borrelia burgdorferi can enter slow-growing or non-growing states under experimental conditions, but how these findings apply to human infection remains an active area of research.

Studies involving Borrelia burgdorferi, the bacterium that causes Lyme disease, have identified antibiotic-tolerant forms commonly called persister cells. These laboratory findings have advanced our understanding of bacterial biology, but they do not by themselves establish how often dormant B. burgdorferi persists in the human body or whether persister cells account for persistent or recurring symptoms in every patient.

What Does Dormant Lyme Disease Mean?

The term “dormant Lyme disease” is widely used by patients, but it does not have a single accepted medical definition. Depending on the situation, it may describe:

An infection that causes few or no noticeable symptoms for a period of time.
Symptoms that improve and later return.
Bacteria entering a slow-growing or non-growing state.
Persistent symptoms after treatment for Lyme disease.
A previously unrecognized infection diagnosed months or years after exposure.

These situations are not necessarily caused by the same biological process. Delayed diagnosis may reflect subtle early symptoms or lack of a recognized tick bite. Readers may also find it helpful to learn why Lyme disease tests can be negative early. In other patients, persistent symptoms may relate to residual tissue injury, immune or neurologic dysfunction, reinfection following another tick bite, coinfections, or other medical conditions. Laboratory studies of bacterial dormancy provide one possible biologic explanation for how bacteria survive stressful conditions, but applying these findings to individual patients remains complex.

What Are Borrelia Persister Cells?

Persister cells are a small subpopulation of bacteria that enter a slow-growing or nondividing state. Because many antibiotics work best against actively dividing bacteria, persister cells may temporarily tolerate antibiotic exposure without developing traditional genetic antibiotic resistance.

Readers interested in persistent symptoms after treatment may also find our article on Post-Treatment Lyme Disease Syndrome (PTLDS) helpful.

Feng and colleagues from Johns Hopkins University evaluated combinations of FDA-approved antibiotics against stationary-phase Borrelia burgdorferi persisters in laboratory cultures.² As the bacteria entered stationary phase, they developed increasing numbers of round bodies and biofilm-like microcolonies, both of which were more tolerant of antibiotics than actively growing spirochetes.

The investigators found that combinations containing daptomycin, cefoperazone, and doxycycline demonstrated greater activity against persister forms in vitro than doxycycline alone. In laboratory subculture experiments, this three-drug combination prevented regrowth of the most antibiotic-tolerant microcolony forms.²

What This Research Does—and Does Not Show

The Feng study provides important insight into the biology of Borrelia burgdorferi, but its findings should be interpreted carefully. This was an in vitro laboratory study, not a clinical trial involving patients with Lyme disease.

The study demonstrated that B. burgdorferi can develop antibiotic-tolerant persister forms under laboratory conditions and that certain antibiotic combinations were more effective than others against these forms in culture. However, it did not establish that persister cells routinely remain in patients after treatment or that they are responsible for persistent symptoms. The authors specifically concluded that additional animal studies and human clinical trials are needed before applying these laboratory findings to patient care.²

Persistence May Be Part of a Dormancy Continuum

Persistence may represent one part of a broader spectrum of bacterial dormancy. According to Mali and colleagues, evidence suggests that dormancy consists of a continuum of interrelated states that includes both viable but nonculturable (VBNC) cells and persister cells.¹

The authors explain that VBNC cells and persister cells may contribute to antibiotic tolerance, the reemergence of latent infections, quorum sensing, and biofilm formation.

Although the Mali study investigated Micrococcus luteus rather than Borrelia burgdorferi, it provides a useful conceptual framework for understanding bacterial dormancy and the challenges researchers face when distinguishing between different non-growing bacterial states.

Persister Cells vs. Viable but Nonculturable (VBNC) Cells

Mali and colleagues distinguish between two related but biologically distinct dormant bacterial states that may help explain how microorganisms survive environmental stress and antibiotic exposure.¹

Persister cells are a small subpopulation of bacteria that spontaneously enter a dormant, nondividing state. They remain capable of resuming growth once stressful conditions resolve and are defined by their ability to survive antibiotic treatment without acquiring genetic antibiotic resistance.
Viable but nonculturable (VBNC) cells are living bacteria that remain metabolically active but lose the ability to grow on routine laboratory culture media.

Mali acknowledges that distinguishing between persister cells and VBNC cells is challenging because both exhibit enhanced survival during antibiotic treatment. The two states may coexist and contribute to reduced metabolic activity, antibiotic tolerance, latent infection, and the reemergence of active bacterial growth after environmental stress has resolved.¹

How Researchers Distinguish the Two States

To provide a clearer framework for future research, Mali and colleagues proposed separate definitions for persister cells and VBNC cells:

Persister cells are proliferation-competent cells that can spontaneously resume growth after stressful conditions have resolved.
VBNC cells enter a non-proliferative state in response to external stress and generally require a specific environmental signal before growth resumes.

Although these concepts were developed from bacterial dormancy research rather than studies of Borrelia burgdorferi alone, they provide investigators with a useful framework for understanding how bacteria may survive unfavorable conditions while becoming difficult to detect or eliminate.

Why This Research Matters

Research into bacterial dormancy has expanded our understanding of how microorganisms survive antibiotics and other environmental stresses. Identifying the proteins and molecular pathways that regulate entry into and exit from dormant states may eventually improve laboratory models of Borrelia burgdorferi persistence and help researchers develop more effective treatment strategies.

The Feng study also demonstrated that different forms of B. burgdorferi vary in their susceptibility to antibiotics. Actively growing spirochetes were the most susceptible, while stationary-phase round bodies and biofilm-like microcolonies exhibited progressively greater antibiotic tolerance under laboratory conditions.²

At present, however, Borrelia persisters remain an active area of investigation. Laboratory findings should not be interpreted as proof that dormant organisms are responsible for persistent symptoms in every patient with Lyme disease. Additional animal studies and human clinical trials are needed to determine how these experimental observations apply to clinical practice.²

Clinical Perspective

In my office practice, patients frequently ask whether Lyme disease can remain dormant for years before symptoms develop or recur. Laboratory studies have demonstrated that Borrelia burgdorferi can adopt slow-growing and antibiotic-tolerant states under experimental conditions. These studies provide important biologic insights, but translating laboratory findings to individual patients remains challenging.

Some patients may have delayed diagnosis because early symptoms were mild or unrecognized. Others may have persistent infection, reinfection from another tick bite, post-treatment Lyme disease syndrome (PTLDS), coinfections such as Babesia or Bartonella, immune-mediated illness, or an unrelated medical condition. Each possibility deserves careful clinical evaluation rather than assuming a single explanation.

When evaluating patients with suspected late or persistent Lyme disease, I rely on a careful clinical history, physical examination, laboratory testing when appropriate, possible tick exposure, response to previous treatment, and consideration of alternative diagnoses rather than any single laboratory finding.

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Frequently Asked Questions

Can Lyme disease lay dormant for years?

Some patients are diagnosed months or years after a tick bite because early infection may have gone unrecognized or symptoms were mild. Laboratory studies suggest that Borrelia burgdorferi can develop slow-growing and antibiotic-tolerant forms under experimental conditions, but how these findings apply to human infection remains an area of ongoing research.

How long can Lyme disease stay dormant?

There is no established time limit for a dormant state in humans. Delayed diagnosis may reflect an initially unrecognized infection, subtle early symptoms, persistent infection, reinfection, or other biological mechanisms. Researchers continue to investigate the role of bacterial dormancy in Lyme disease.

What are Borrelia persister cells?

Persister cells are a small population of bacteria that enter a slow-growing or nondividing state. Because many antibiotics target actively dividing bacteria, persister cells may temporarily tolerate antibiotic exposure without developing true genetic antibiotic resistance.

What is the difference between persister cells and viable but nonculturable (VBNC) cells?

Persister cells can spontaneously resume growth once favorable conditions return. In contrast, viable but nonculturable (VBNC) cells generally require a specific external signal before they regain the ability to grow. Both states remain active areas of bacterial dormancy research.

Does research on Borrelia persisters prove dormant Lyme disease causes persistent symptoms?

No. Laboratory studies have demonstrated persister forms of Borrelia burgdorferi, but they do not prove that these bacterial forms routinely persist in patients after treatment or explain persistent symptoms in every individual with Lyme disease. Additional animal studies and human clinical research are needed.

Clinical Takeaway

Research into Borrelia burgdorferi persisters has expanded our understanding of how bacteria survive environmental stress and antibiotic exposure under laboratory conditions. These studies have identified slow-growing and antibiotic-tolerant bacterial states that may contribute to persistence in culture and provide valuable models for future investigation.

In my office practice, patients frequently ask whether Lyme disease can remain dormant for years before symptoms appear or recur. Laboratory findings have advanced our understanding of bacterial biology, but they should be interpreted cautiously when applied to individual patients. Clinical decisions should continue to rely on a careful history, physical examination, appropriate laboratory testing, possible tick exposure, response to previous treatment, and consideration of alternative diagnoses.

Current evidence supports the existence of Borrelia burgdorferi persister cells in laboratory studies. Determining whether these bacterial states contribute to persistent or recurrent illness in humans remains an important area of ongoing clinical research.

Learn more about persistent symptoms, diagnosis, and recovery:

Persistent Lyme Disease: Symptoms and Treatment
Lyme Disease Misdiagnosis
Why Lyme Disease Tests Can Be Negative Early
Understanding Lyme Disease Test Accuracy