Lyme Persister Cells: What They Are and Why They Matter
Persister cells can survive antibiotic exposure in laboratory models
Antibiotic tolerance is different from inherited antibiotic resistance
Their role in persistent symptoms after Lyme disease remains uncertain
Why do some Lyme disease symptoms continue after treatment? One explanation under investigation involves Lyme persister cells—a small subpopulation of Borrelia burgdorferi that can survive exposure to antibiotics under laboratory conditions.
These findings offer a biologically plausible explanation for antibiotic tolerance. However, laboratory evidence does not establish that persister cells are responsible for persistent symptoms in an individual patient.
Persister cells are one of several proposed mechanisms of persistent illness after Lyme disease.
What Are Lyme Persister Cells?
Persister cells are temporary, drug-tolerant members of a bacterial population. They can survive antibiotic exposure without necessarily carrying inherited genetic resistance.
Some persister cells have low metabolic activity or enter a non-growing state. Because many antibiotics work most effectively against actively growing bacteria, these cells may be less susceptible while they remain inactive.
When surviving cells resume growth, their descendants may again become susceptible to the same antibiotics. This distinguishes persister cells from bacteria with stable, inherited antibiotic resistance.
Antibiotic Tolerance Is Not the Same as Resistance
Persister cells demonstrate antibiotic tolerance rather than conventional antibiotic resistance.
- Antibiotic resistance usually involves an inherited genetic change that allows bacteria to grow despite an antibiotic.
- Antibiotic tolerance allows some bacteria to survive exposure temporarily without necessarily growing.
- Persistence describes the survival of a small drug-tolerant subpopulation within a larger bacterial population.
In a laboratory study, surviving Borrelia burgdorferi cells produced new populations containing both antibiotic-susceptible and drug-tolerant cells. This behavior supported their classification as persisters rather than genetically resistant mutants.
Are Round Bodies and Microcolonies Persister Cells?
Borrelia burgdorferi can develop different morphologic forms under laboratory conditions, including:
- Actively growing spirochetes
- Round-body forms
- Microcolony-like aggregates
Older cultures containing round bodies and microcolonies have demonstrated greater antibiotic tolerance in some experiments. However, these morphologic forms should not automatically be considered synonymous with persister cells.
Morphology describes what the bacteria look like, while persistence describes how a subpopulation survives antimicrobial exposure. The two concepts may overlap, but they are not interchangeable.
Researchers have also investigated biofilm-like aggregates in Lyme disease. Their clinical significance in human infection remains uncertain.
Why Persister Cells May Survive Antibiotics
Several mechanisms may contribute to bacterial persistence:
- Reduced metabolic activity
- Temporary interruption of bacterial growth
- Activation of stress-response pathways
- Changes in gene expression
- Differences in antibiotic susceptibility within the bacterial population
These survival strategies may allow a small portion of a bacterial population to remain viable when more actively growing cells are eliminated.
What Laboratory Studies Have Found
Laboratory studies have demonstrated that stationary-phase cultures of Borrelia burgdorferi contain cells that tolerate antibiotics commonly active against growing spirochetes.
Researchers have tested several antimicrobial combinations against these cultures. One frequently cited in vitro study found activity from a three-drug combination containing:
- Daptomycin
- Doxycycline
- Cefoperazone
The combination eliminated viable organisms from the study’s laboratory cultures, including microcolony forms that were more tolerant of individual antibiotics.
These were laboratory experiments—not clinical treatment trials. The concentrations, combinations, and conditions used in a laboratory culture cannot automatically be translated into safe or effective treatment for patients.
Do Persister Cells Explain Persistent Lyme Symptoms?
Persister cells provide a possible biological hypothesis, but their role in human illness has not been established.
Current research has not determined:
- How often drug-tolerant Borrelia cells remain after treatment in people
- Whether persister cells directly cause ongoing symptoms
- Whether laboratory findings predict clinical treatment response
- Which patients, if any, would benefit from treatments targeting persisters
- Which drug combinations would be safe and effective in clinical practice
There is also no routinely available clinical test that can identify Lyme persister cells in an individual patient.
Persister Cells and Lyme Disease Treatment
Laboratory findings have encouraged research into drugs and combinations that might act against both growing and non-growing bacterial populations.
However, these findings should not be interpreted as evidence that experimental combinations are proven Lyme disease treatments. Some drugs tested in vitro can produce serious adverse effects and may not reach the same concentrations safely in the human body.
The research helps explain why scientists continue to investigate different bacterial states and treatment responses. It does not yet establish a standard clinical protocol for eliminating Lyme persister cells.
Learn more about why patients may respond differently to Lyme disease treatment.
Other Explanations for Persistent Symptoms
Persistent symptoms after Lyme disease may have more than one contributing factor. Possibilities under investigation include:
- Ongoing inflammation
- Immune system dysregulation
- Tissue injury from the original infection
- Neurologic or autonomic dysfunction
- Metabolic or endocrine disorders
- Medication effects
- Another unrelated medical condition
- Tick-borne co-infections
These explanations are not mutually exclusive. Different mechanisms may contribute to similar symptoms in different patients.
How This Research Relates to Patients
Patients may experience fatigue, pain, cognitive difficulties, neurologic symptoms, or other problems that continue after treatment. These symptoms deserve a careful clinical evaluation, but they cannot by themselves establish the presence of persister cells.
Read more about persistent Lyme disease symptoms after treatment.
Some patients improve and later experience recurrent symptoms. See why Lyme disease symptoms may return.
Symptoms can also fluctuate over time. Learn more about why Lyme disease symptoms may come and go.
Clinical Perspective
Research into Lyme persister cells helps explain how genetically susceptible bacteria may survive antibiotic exposure under laboratory conditions. It also highlights the biological diversity that can exist within a single bacterial population.
Nevertheless, persistent or recurrent symptoms are not proof that viable bacteria remain. Clinical decisions should consider the patient’s history, examination, previous treatment, possible co-infections, alternative diagnoses, and the limitations of currently available tests.
Clinical Takeaway
Laboratory studies show that a subpopulation of Borrelia burgdorferi can tolerate antibiotic exposure without developing conventional inherited resistance.
These persister cells may help researchers understand why bacterial populations respond differently to treatment. However, their contribution to persistent symptoms in patients remains uncertain, and no established clinical test can determine whether an individual patient has Lyme persister cells.
Frequently Asked Questions
What are Lyme persister cells?
Lyme persister cells are a small subpopulation of Borrelia burgdorferi that can survive antibiotic exposure under laboratory conditions. Their survival reflects temporary antibiotic tolerance rather than necessarily inherited resistance.
Are persister cells resistant to antibiotics?
Not in the conventional genetic sense. Persister cells may temporarily tolerate an antibiotic while they are inactive or growing slowly. When they resume growth, their descendants may again be susceptible to the same antibiotic.
Do Lyme persister cells cause chronic symptoms?
That has not been established. Laboratory studies demonstrate drug-tolerant Borrelia populations, but researchers have not determined how often they occur in treated patients or whether they directly cause persistent symptoms.
Can doctors test patients for Lyme persister cells?
No routinely available clinical test can determine whether an individual patient has Lyme persister cells.
Are there proven treatments for Lyme persister cells?
No treatment has been established specifically for Lyme persister cells through adequate clinical trials. Drug combinations that show activity in laboratory cultures should not automatically be considered safe or effective treatments for patients.
References
Sharma B, Brown AV, Matluck NE, Hu LT, Lewis K. Borrelia burgdorferi, the causative agent of Lyme disease, forms drug-tolerant persister cells. Antimicrob Agents Chemother. 2015;59(8):4616–4624.
Feng J, Auwaerter PG, Zhang Y. Drug combinations against Borrelia burgdorferi persisters in vitro: eradication achieved by using daptomycin, cefoperazone and doxycycline. PLoS One. 2015;10(3):e0117207.
Caskey JR, Embers ME. Persister development by Borrelia burgdorferi populations in vitro. Antimicrob Agents Chemother. 2015;59(10):6288–6295.
This article is for educational purposes and does not provide individual medical advice. Experimental laboratory findings should not be used to select treatment without guidance from a qualified clinician.
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
