Bacterial Mechanism That Could Help Prevent and Treat Lyme Arthritis Identified by New Bay Area Lyme Foundation–Supported Study
Research published in PLOS Pathogens highlights a cell wall–driven trigger of joint inflammation, pointing to new ways to target Lyme arthritis
Bay Area Lyme Foundation, a leading sponsor of Lyme disease research in the United States, announced the publication of new research in PLOS Pathogens identifying a novel mechanism that may trigger Lyme arthritis, one of the most common and debilitating complications of Lyme disease in the US. The study provides new insight into how the structure of Borrelia burgdorferi peptidoglycan, a component of the bacterium’s cell wall, and its interaction with a Borrelia protein can provoke joint inflammation. In a preclinical model, subtle changes researchers made to the bacterium’s peptidoglycan structure nearly eliminated arthritis despite ongoing infection, suggesting new approaches to reduce Lyme arthritis and joint damage that may complement antibiotics by targeting inflammatory bacterial components.
“Understanding how these bacterial structures provoke inflammation is an avenue towards new approaches for limiting long-term joint damage and possibly treating patients whose symptoms persist despite standard antibiotic therapy,” said Brandon L. Jutras, PhD, lead author of the study and associate professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine, and a Bay Area Lyme Foundation 2021 Emerging Leader Award winner. “Our findings offer critical insight into how Lyme arthritis is largely driven by specific structural components of Borrelia burgdorferi that may be targeted independent of the other aspects of the infection.”
This new study demonstrates that the chemical makeup and physical structure of peptidoglycan, a structural component of the Borrelia cell wall, play a decisive role in determining whether joint inflammation develops. It also demonstrates how impeding peptidoglycan’s interaction with a specific Borrelia protein may impact the bacterium’s ability to migrate to and persist within joint tissue, resulting in near elimination of Lyme arthritis in the study.
“This research represents a major advance in understanding the biological drivers of Lyme arthritis and underscores the importance of identifying and supporting innovative scientists early in their careers,” said Linda Giampa, Board of Directors, Bay Area Lyme Foundation. “By investing in Dr. Jutras’ research through our Emerging Leader Award, we helped accelerate discoveries that now point toward new therapeutic approaches with real potential to provide better treatment options for patients.”
Previous research by Jutras and his team has shown that peptidoglycan can linger in joint tissue and drive chronic inflammation.
(Editor’s note: the role of peptidoglycans in joint inflammation has been raised previously. Some researchers are attempting to use these findings to support the existence of symptoms persisting after treatment for Lyme disease, known as post-treatment Lyme disease syndrome. However, no study has been able to prove that the chronic symptoms persisting after treatment are not caused by the persistent presence of the pathogen – the simplest explanation for the persistence of peptidoglycans is that the pathogen itself is persistently present. No tests were carried out to rule out the presence of the pathogen.)
However, why this process leads to severe arthritis in some patients, but not others, has remained unclear until this study. In this new study, the researchers genetically altered B. burgdorferi to subtly change the structure of its peptidoglycan. The modified bacteria caused little to no joint inflammation in preclinical models of infection. This is in sharp contrast to animals infected with unmodified bacteria despite similar levels of infection throughout the body.
Altering the structure of peptidoglycan also disrupted a previously unrecognized interaction between peptidoglycan and p83/100, an immunodominant Borrelia protein that has been associated with joint involvement in Lyme disease in past studies. These findings help explain why bacterial remnants can be detected in patients’ joints years after infection and show that it is not just the presence of bacterial remnants, but how they are structured and how they interact with the immune system, that drives disease.
p83/100 is one of Borrelia’s immunologically dominant proteins, which previous research has already linked to joint involvement in Lyme disease.
The study also highlights that it is not merely the presence of bacterial remnants that causes the disease, but that the structure of these bacterial structures and how they interact with the immune system are also key factors.
This finding may open up new avenues of research into targeted treatment for Lyme arthritis, particularly for patients whose symptoms of joint inflammation persist even after completing a course of antibiotics.
(C) Lyme Borreliosis Foundation
