Lyme Bacterial Fragments May Persist After Infection
Lyme bacterial fragments may persist in tissues after infection.
Cell-wall material may continue interacting with the immune system.
The findings raise questions about persistent symptoms and inflammation.
Lyme bacterial fragments may persist in tissues after infection and continue to stimulate the immune system, according to research examining cell-wall material from Borrelia burgdorferi, the bacterium that causes Lyme disease.
The study adds to growing evidence that persistent symptoms after Lyme disease may arise from multiple mechanisms, including lingering bacterial antigens, ongoing immune activation, tissue inflammation, altered metabolism, autoimmunity, co-infections, and—in some patients—the possibility of persistent infection.
This distinction matters. Patients with persistent symptoms are often told that there is no clear biologic explanation once standard antibiotic treatment has been completed. However, studies of Borrelia peptidoglycan suggest that bacterial material may remain biologically active long after the initial infection.
Researchers emphasize that these findings do not prove persistent infection. Instead, they demonstrate that components of the Lyme disease bacterium can persist and continue interacting with the immune system, providing another biologically plausible explanation for persistent symptoms in some patients.
What Are Lyme Bacterial Fragments?
Peptidoglycan is a structural component of the bacterial cell wall. In Borrelia burgdorferi, this material has unusual chemical features that appear to make it more resistant to clearance than peptidoglycan from many other bacterial species.
Earlier work by Jutras and colleagues identified Borrelia burgdorferi peptidoglycan in the synovial fluid of patients with Lyme arthritis, suggesting that bacterial cell-wall material may persist within inflamed joints even after the initial infection has been treated.
The newer investigation extends this work by asking whether Borrelia peptidoglycan can also persist outside the joints and alter immune or metabolic pathways in other tissues.
What the New Study Found
Researchers created two forms of Borrelia burgdorferi peptidoglycan in a mouse model.
Small peptidoglycan fragments were cleared within several days. Larger fragments, however, accumulated in the liver and remained detectable for at least four weeks.
This prolonged persistence appeared to be unusual for Borrelia burgdorferi. Comparable peptidoglycan from several other bacterial species was eliminated much more rapidly.
The investigators also observed altered liver protein expression and elevated blood markers associated with liver dysfunction. Approximately 70% of the proteins whose expression changed were involved in immune-related pathways.
Together, these findings suggest that Borrelia cell-wall material may do more than simply remain within tissues. It may continue interacting with the immune system and influence inflammatory and metabolic processes long after the initial infection.
Why This May Matter for Persistent Lyme Symptoms
Patients with persistent symptoms following Lyme disease frequently report fatigue, musculoskeletal pain, cognitive difficulties, and reduced physical function. The underlying causes remain the subject of ongoing investigation.
One proposed mechanism is that bacterial fragments remaining after infection continue to stimulate the immune system, even if viable organisms are no longer easily detected.
Other proposed mechanisms include persistent immune activation, metabolic dysregulation, autoimmunity, co-infections, autonomic dysfunction, and, in selected patients, persistent infection.
The study does not resolve this debate. However, it provides additional biologic evidence that Borrelia peptidoglycan can persist in tissues and continue to activate immune pathways, offering a plausible mechanism that may contribute to persistent symptoms in at least some patients.
How Could Bacterial Fragments Keep Inflammation Going?
A 2025 review of Lyme arthritis describes several ways inflammation may continue. Bacterial antigens, including peptidoglycan, may activate innate and adaptive immune responses even when viable organisms are not detected.
The review also discusses the “amber hypothesis,” in which nonviable spirochetes or bacterial debris may become trapped within a host-derived matrix near affected tissue. This material could provide a continuing focus for inflammation while it remains uncleared.
Other immune pathways may also become poorly regulated or self-perpetuating. Molecular mimicry and autoimmune reactions have been proposed, but their clinical significance has not been conclusively established.
These possibilities are not mutually exclusive. Persistent bacterial material, immune dysregulation, tissue injury, and other mechanisms may contribute differently from one patient to another.
Could These Fragments Come From an Ongoing Infection?
One important question remains unanswered: Where do these lingering bacterial fragments come from?
The investigators demonstrated that Borrelia burgdorferi peptidoglycan can persist in tissues and remain biologically active. However, the study was not designed to determine whether these fragments originated solely from bacteria killed during the initial infection or whether some patients might continue generating new fragments from an ongoing infection.
This distinction is clinically important.
Answering this question will likely require future studies that simultaneously evaluate persistent bacterial antigens, evidence of viable organisms, and the host immune response over time.
If bacterial fragments simply persist after the infection has been cleared, therapies designed to remove or neutralize these inflammatory fragments could eventually become an important treatment strategy.
However, if new fragments continue to be produced because viable Borrelia organisms remain in some patients, then eliminating fragments alone may not adequately address the underlying disease process.
The current study supports persistent peptidoglycan as one biologically plausible mechanism for ongoing inflammation. It neither proves nor excludes persistent infection, and it does not rule out other contributing mechanisms.
Persistent symptoms after Lyme disease are likely multifactorial and may involve residual bacterial antigens, immune dysregulation, chronic inflammation, altered metabolism, autoimmunity, co-infections, autonomic dysfunction, persistent infection, or combinations of these processes.
Why the Liver Finding Is Important
Previous research focused primarily on Borrelia peptidoglycan within inflamed joints of patients with Lyme arthritis.
The newer study broadens that perspective by demonstrating that bacterial cell-wall fragments may also persist outside the joints, particularly within the liver.
The liver plays a central role in metabolism, immune regulation, detoxification, and inflammatory signaling. Persistent Borrelia peptidoglycan within the liver could therefore influence systemic immune responses rather than simply causing localized inflammation.
The investigators also identified alterations in proteins involved in energy metabolism. This observation is particularly interesting because persistent fatigue is commonly reported by patients with ongoing illness after Lyme disease.
Because these findings were generated primarily in a mouse model, additional human studies are needed before their clinical significance can be determined. Nevertheless, the study provides mechanistic insight into how persistent bacterial products could contribute to prolonged inflammation.
What This Study Does Not Prove
The study does not prove that peptidoglycan fragments are the sole cause of post-treatment Lyme disease syndrome.
It also does not demonstrate that every patient with persistent symptoms has lingering bacterial fragments within the liver or other tissues.
Importantly, it does not rule out persistent infection as a contributor in selected patients.
Instead, the study adds another piece to the complex puzzle of persistent Lyme disease. Borrelia burgdorferi may leave behind biologically active cell-wall material that persists longer than expected and may continue influencing immune and metabolic pathways after infection.
Frequently Asked Questions
What are Lyme bacterial fragments?
Lyme bacterial fragments are pieces of Borrelia burgdorferi, including peptidoglycan from the bacterial cell wall, that may remain in tissues after infection and continue interacting with the immune system.
Do Lyme bacterial fragments prove there is still an active infection?
No. Persistent bacterial fragments may remain after bacteria have been eliminated. However, their presence does not exclude the possibility of ongoing infection in selected patients.
Can Lyme bacterial fragments cause inflammation?
Research suggests that Borrelia burgdorferi peptidoglycan can stimulate immune responses and may contribute to persistent inflammation.
Does this explain post-treatment Lyme disease syndrome?
Persistent bacterial fragments represent one biologically plausible mechanism among several that may contribute to persistent symptoms after Lyme disease.
Should this change treatment now?
Not yet. Additional human studies are needed before these findings can guide routine clinical treatment.
Clinical Takeaway
Research suggests that Borrelia burgdorferi cell-wall fragments may persist in tissues and continue stimulating immune and metabolic pathways after the initial infection.
These findings provide biologic evidence that persistent bacterial products may contribute to inflammation after Lyme disease. However, they neither prove nor exclude persistent infection in selected patients.
Distinguishing persistent bacterial antigens from viable organisms will be important for developing more targeted treatments for patients with ongoing Lyme disease symptoms.
Related Articles
Persistent Lyme disease symptoms may involve immune activation, neurologic dysfunction, inflammation, metabolic changes, and infectious mechanisms. These related articles explore those topics in greater detail.
Persistent Lyme Disease Mechanisms
Post-Treatment Lyme Disease Syndrome (PTLDS)
Persistent Lyme Disease Overview
Lyme Disease Fatigue
Recovery From Lyme Disease
References
- Jutras BL, Lochhead RB, Kloos ZA, Biboy J, Strle K, Booth CJ, Govers SK, et al. Borrelia burgdorferi peptidoglycan is a persistent antigen in patients with Lyme arthritis. Proc Natl Acad Sci U S A. 2019;116(27):13498–13507.
- McClune ME, DeHart TG, Dotsey EY, et al. Borrelia burgdorferi peptidoglycan persists in the liver and promotes immune and metabolic dysfunction. Sci Transl Med. 2025;17(795):eadr2955.
- DeHart TG, Booth CJ, Hickey KL, et al. Lyme disease spirochetes alter peptidoglycan structure to evade innate immune recognition. Nat Microbiol. 2021;6(12):1583–1592.
- Sigal LH. Aspects of the immunopathogenesis of Lyme arthritis. Microorganisms. 2025;13(7):1602.
This article is for informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment.
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
Informative as usual. Thanks for posting.