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It is increasingly recognized that symptoms can persist long after the standard treatment for Lyme disease, with a recent study revealing that 14% of individuals diagnosed and successfully treated with antibiotics still develop Post Treatment Lyme Disease (PTLD). The precise mechanisms behind these lingering symptoms, which can include debilitating fatigue, cognitive difficulties, and joint pain, remain elusive to many physicians.
Researchers at Northwestern University have proposed a novel explanation for this phenomenon, suggesting that remnants of the bacterial cell wall from Borrelia burgdorferi—the bacterium responsible for Lyme disease—may trigger the body’s immune response. According to their findings, although treatment reduces the presence of the bacteria, remnants persist in the liver, leading to a response similar to what is seen in long COVID-19, where residual viral particles provoke an excessive immune reaction, as explained by bacteriologist Brandon L. Jutras.
“While Lyme disease and long COVID-19 are fundamentally different, they might share a common inflammatory mechanism linked to the remnants of an earlier infection,” Jutras stated, highlighting that the immune system’s overreaction might not always be due to ongoing infection.
Peptidoglycan, a vital component of bacterial cell walls and a target for many antibiotics, including penicillin, has been a focal point in ongoing research. The team tracked the movement of peptidoglycan from various bacterial strains in real-time and noted that, unlike other bacteria that quickly shed their cell wall material, the peptidoglycan associated with Lyme disease lingers for weeks or months post-treatment.
Among the chronic effects of Lyme disease, Lyme arthritis is particularly notable. For example, a swollen knee, often filled with synovial fluid, harbors fragments of peptidoglycan long after antibiotic treatment has ended. Jutras observed that while anti-inflammatory medications can help alleviate symptoms in these patients, they do not always respond positively to antibiotic treatments, suggesting that genetic factors may play a role in individual patient responses.
Jutras, who has dedicated over 15 years to studying Lyme disease, currently serves as an associate professor at Northwestern University Feinberg School of Medicine and is a member of the Center for Human Immunobiology. He began his research journey during graduate studies and previously worked as an associate professor at Virginia Tech University.
He described peptidoglycan as a protective barrier for bacteria, akin to a structural skeleton. Antibiotics effectively target the synthesis of this molecule because it is specific to bacterial cells. The uniqueness of Lyme’s peptidoglycan may explain its resilience in human hosts. Unlike that of other bacteria, Lyme peptidoglycan has special structural characteristics that may allow it to cling to human tissues and evade clearance.
Upon the death of the bacteria—whether by antibiotics or immune response—these modified peptidoglycan components tend to accumulate in the liver, unable to be metabolized. Jutras suggested that if the peptidoglycan were not modified, it would likely be eliminated from the body as seen after other infections.
“The unique chemical nature of Lyme’s peptidoglycan supports its persistence, but it is the individual’s immune response that significantly determines the clinical outcomes,” he stated. Some patients may react with a strong immune response that exacerbates their symptoms, while others may have a milder reaction, indicating that the presence of the molecule alone does not dictate the disease’s trajectory.
Looking ahead, Jutras aims for these pivotal findings to inspire the creation of more precise diagnostic tests for PTLD and to improve treatment strategies for individuals who do not respond to antibiotics. Instead of merely focusing on eradicating an infection that may no longer be active, research is shifting towards targeting the inflammatory molecules involved, including the potential use of monoclonal antibodies designed to destroy peptidoglycan.
This research has received backing from several organizations, including the National Institutes of Allergy and Infectious Diseases, the Steven & Alexandra Cohen Foundation, the Department of Defense, the Global Lyme Alliance, and the Bay Area Lyme Foundation.
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