Persister Cells in Lyme Disease: Why Treatment May Fall Short

Why do some Lyme disease patients remain ill despite appropriate antibiotic treatment?

One explanation under investigation is the presence of persister cells in Lyme disease—a phenomenon increasingly recognized across microbiology.

“Though its applicability to B. burgdorferi has been controversial, persistence is a widely accepted phenomenon in microbiology which in some instances can have therapeutic implications,” according to Cabello. [1]

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

How Persister Cells May Develop

The ability of B. burgdorferi to survive in both ticks and vertebrate hosts may contribute to the development of persister cells.

The metabolic and morphologic changes required for survival across these environments may allow the organism to tolerate otherwise lethal doses of antibiotics.

Spirochetes can become tolerant to antimicrobials through phenotypic changes—adaptations that do not involve genetic mutation.

For example, B. burgdorferi expresses outer surface protein A (OspA) in the tick and outer surface protein C (OspC) in vertebrate hosts.

Evidence from Laboratory Studies

In culture, stationary-phase B. burgdorferi cells demonstrate tolerance to commonly used antibiotics including ceftriaxone, doxycycline, and amoxicillin.

Cabello describes:

“Readily detectable borrelia tolerant to antimicrobials in suspension cultures and biofilms in vitro, potential refugia for persister spirochetes and apparently quiescent round forms under several kinds of environmental stresses.”

These “refugia” may represent protected environments where spirochetes persist.

“Borrelia burgdorferi … can colonize and persist in multiple tissue sites despite vigorous host immune responses,” Cabello previously reported. [2]

Such sites may include collagen-rich or relatively avascular tissues where bacterial activity is reduced.

Clinical Implications

Persistence is considered a phenotypic phenomenon. However, the presence of persister cells may also contribute indirectly to antimicrobial resistance through mutation over time.

While the clinical significance remains under investigation, these findings may help explain why some patients continue to experience symptoms after standard treatment.

For a broader discussion of persistent symptoms, see post-treatment Lyme disease syndrome (PTLDS) and the Lyme disease symptoms guide.

Clinical Takeaway

Persister cells may represent one mechanism behind treatment-resistant Lyme disease. While still under study, this model highlights the complexity of infection and the need for individualized care.

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

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