Lingering Bacterial Debris May Drive Post-Treatment Lyme Symptoms – Neuroscience News
2025-04-24T14:59:30Z
New research suggests that lingering cell wall fragments from the Lyme disease bacterium, Borrelia burgdorferi, may be responsible for persistent symptoms long after antibiotic treatment.
Summary: New research suggests that lingering cell wall fragments from the Lyme disease bacterium, Borrelia burgdorferi, may be responsible for persistent symptoms long after antibiotic treatment. These fragments, made of a unique form of peptidoglycan, appear to accumulate in the liver and joints, triggering inflammation and immune responses even after the infection is gone.
This mechanism resembles theories behind long COVID, where the immune system reacts to residual viral components. The findings could pave the way for targeted treatments and diagnostic tools that focus on inflammation rather than active infection.
Key Facts:
Persistent Debris: Lyme bacteria’s unique peptidoglycan can linger for months post-treatment.
Lyme bacteria’s unique peptidoglycan can linger for months post-treatment. Inflammatory Trigger: These remnants may drive ongoing symptoms like joint pain and fatigue.
These remnants may drive ongoing symptoms like joint pain and fatigue. New Targets: Researchers are exploring monoclonal antibodies to neutralize the leftover molecules.
Source: Northwestern University
Symptoms that persist long after Lyme disease is treated are not uncommon — a 2022 study found that 14% of patients who were diagnosed and treated early with antibiotic therapy would still develop Post Treatment Lyme Disease (PTLD).
Yet doctors puzzle over the condition’s causes and how to help their patients through symptoms ranging from severe fatigue and cognitive challenges to body pain and arthritis.
Now, Northwestern University scientists believe they know what causes the treated infection to mimic chronic illness: the body may be responding to remnants of the Borrelia burgdorferi (the bacteria that causes Lyme) cell wall, which breaks down during treatment yet lingers in the liver.
This matches one theory behind the underlying causes of long COVID-19 in that persisting viral molecules may encourage a strong, albeit unnecessary, immune response, said bacteriologist Brandon L. Jutras.
“Lyme and long COVID-19 are clearly vastly different diseases, but it’s possible that they share a more general mechanism of inappropriate inflammation caused by remnants of a previous infection,” said Jutras, who led the research.
“The maladaptive response is a product of an infection, but perhaps not necessarily an active one in all cases.”
Peptidoglycan is a structural feature of virtually all bacterial cells and a common target of antibiotics, including penicillin.
The research, to be published April 23 in the journal Science Translational Medicine, tracked the biodistribution of peptidoglycan from different bacteria, in real time, and found that all cell wall material is rapidly shed, but Lyme disease’s peptidoglycan persists for weeks to months.
Lyme arthritis is one of the more common long-term impacts of exposure to Lyme. If a patient has a swollen knee, for instance, it is full of synovial fluid, a natural lubricant found in joints. Jutras said his team looked at the fluid in humans and found that pieces of the peptidoglycan were omnipresent weeks to months after treatment.
“In the context of Lyme arthritis, if you give patients anti-inflammatory, disease-modifying antirheumatic drugs, they get better,” Jutras said.
“Some of these very same patients do not get better after oral and IV antibiotics, which implies there is something unique about how patients respond at a genetic level.”
Jutras, who joined Northwestern faculty last summer, is an associate professor of microbiology-immunology at Northwestern University Feinberg School of Medicine and a member of the Center for Human Immunobiology at Northwestern.
He has been studying Lyme disease for more than 15 years, beginning in graduate school, and was previously an associate professor at Virginia Tech University.
“Peptidoglycan is kind of like a structural skeleton in virtually all bacteria, acting as a big protective bag for the bacterium,” Jutras said.
“Penicillin and amoxicillin and dozens of other drugs target peptidoglycan synthesis because it’s a molecule that is specific to bacteria, it has similar structural features across the kingdom, and it’s essential.”
Lyme’s peptidoglycan, however, is structurally unique, and this difference may be behind its persistence in humans. Instead of looking the same as with other bacteria, the Lyme peptidoglycan is fundamentally distinct, which is facilitated in part by sucking up sugars from its tick vector.
Upon bacterial cell death — by antibiotics or the immune system — surviving molecules tend to relocate to the liver, which can’t process the modified peptidoglycan.
Without this modification, it seems likely that the peptidoglycan would clear right away, as in other infections.
“The unusual chemical properties of Borrelia peptidoglycan promote persistence, but it’s the individual patient response to the molecule that likely impacts the overall clinical outcome,” Jutras said.
“Some patients will have a more robust or stronger immune response, which could result in a worse disease outcome, while the immune system of others may largely ignore the molecule.
“So, in essence, it’s not about whether the molecule is there or not, it’s more about how an individual responds to it.”
Jutras hopes the groundbreaking findings will lead to development of more accurate tests, possibly for PTLD patients, and refined treatment options when antibiotics have failed.
To effectively stymie PTLD, instead of neutralizing an infection that may no longer exist, efforts are underway to neutralize the inflammatory molecule, including weaponizing monoclonal antibodies to target peptidoglycan for destruction.
Funding: The research was supported by the National Institutes of Allergy and Infectious Diseases (R21AI159800, R01AI173256, R01AI178711), the Steven & Alexandra Cohen Foundation, the Department of Defense (TB220039), the Global Lyme Alliance and the Bay Area Lyme Foundation.
About this neurology and Lyme disease research news
Author: Win Reynolds
Source: Northwestern University
Contact: Win Reynolds – Northwestern University
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“The peptidoglycan of Borrelia burgdorferi can persist in discrete tissues and cause systemic responses consistent with chronic illness” by Brandon L. Jutras et al. Science Translational Medicine
Abstract
The peptidoglycan of Borrelia burgdorferi can persist in discrete tissues and cause systemic responses consistent with chronic illness
Persistent symptoms after an acute infection is an emerging public health concern, but the pathobiology of such conditions is not well understood. One possible scenario involves the persistence of lingering antigen.
We have previously reported that patients with postinfectious Lyme arthritis often harbor the peptidoglycan (PG) cell wall of Borrelia burgdorferi, the Lyme disease agent, in the synovial fluid of their inflamed joints after treatment.
However, it is not yet known how B. burgdorferi PG persists, in what form, or if it may play a role in other postinfectious complications after Lyme disease.
Using a murine model, we developed a real-time in vivo system to track B. burgdorferi PG as a function of cell wall chemistry and validated our findings using both molecular and cellular approaches.
Unlike typical bacterial PG, the unique chemical properties of polymeric B. burgdorferi PG drive murine liver accumulation, where the cell wall material persists for weeks.
Kupffer cells and hepatocytes phagocytose and retain B. burgdorferi PG and, although liver occupancy coincides with minimal pathology, both organ-specific and secreted protein profiles produced under these conditions bear some similarities to reported proteins enriched in patients with chronic illness after acute infection.
Moreover, transcriptomic profiling indicated that B. burgdorferi PG affects energy metabolism in peripheral blood mononuclear cells.
Our findings provide mechanistic insights into how a pathogenic molecule can persist after agent clearance, potentially contributing to illness after infection.
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