Lyme Arthritis: How Persistent Peptidoglycan May Drive Inflammation
Persistent bacterial components may contribute to Lyme arthritis
Peptidoglycan and NapA may amplify inflammation
Researchers are exploring future diagnostic and treatment targets
Lyme arthritis can persist in some patients after initial antibiotic treatment. Researchers are investigating whether persistent bacterial components, including peptidoglycan, may continue to stimulate inflammation.
Findings from this latest study are a “testament to how unique this bacterium is — and how we need to keep working to understand more about what is going on behind the scenes in order to develop future diagnostics and treatments,” states Mari Davis, lead author on the paper.
In earlier studies, Brandon Jutras, a Virginia Tech biochemist, discovered that as the Lyme disease bacterium Borrelia burgdorferi multiplies, it sheds a cellular component called peptidoglycan that elicits a unique inflammatory response in the body.1
Peptidoglycan, he reported, contributes to inflammation and Lyme arthritis.
Peptidoglycan is an essential component of bacterial cell walls. It remained detectable in some patients with Lyme arthritis weeks to months after the initial infection and may have continued to stimulate inflammation.
The source of persistent peptidoglycan remains uncertain. It may represent bacterial material that persists after organisms have been cleared, but the possibility that persistent Borrelia burgdorferi infection continues to produce or replenish these inflammatory components has not been excluded. Other tick-borne infections may contribute to ongoing symptoms or inflammation in individual patients, although they would not account for the presence of Borrelia burgdorferi peptidoglycan or NapA, and these studies did not investigate coinfections.
NapA protein may influence the immune response
More recently, scientists in the Jutras laboratory, led by Brandon Jutras, identified a peptidoglycan-associated protein called Neutrophil Attracting Protein A (NapA) in the bacterium Borrelia burgdorferi.
“Using microfluidics, we demonstrate that NapA acts as a molecular beacon—exacerbating the pathogenic properties of B. burgdorferi [peptidoglycan].”2
NapA is an “immunomodulatory molecule that is able to recruit immune cells, called neutrophils, toward the inflammatory peptidoglycan,” the authors explain.
“NapA is another piece to an ever-evolving puzzle; it seems to play a basic role in everyday bacterial life by helping the overall protective properties of peptidoglycan,” explains Jutras, “but it moonlights as a devious protein capable of tricking our immune system.”
NapA may play different roles during infection
“Early in infection, when bacteria are dying and releasing NapA and peptidoglycan, it acts as a decoy to attract immune cells, which allows the viable bacteria to escape and cause disease,” Jutras explains.
“In later stages of disease, it may act to attract immune cells to peptidoglycan, a molecule capable of causing inflammation and arthritis.”
Frequently Asked Questions
What is peptidoglycan in Lyme disease?
Peptidoglycan is a structural component of the bacterial cell wall. Research suggests that peptidoglycan from Borrelia burgdorferi may persist in some patients with Lyme arthritis and continue stimulating inflammation.
What is the NapA protein?
Neutrophil Attracting Protein A (NapA) is a protein associated with Borrelia burgdorferi peptidoglycan. Laboratory findings suggest that it may attract neutrophils toward peptidoglycan and amplify the inflammatory response.
Does persistent peptidoglycan prove that Lyme infection is still present?
Not by itself. Persistent peptidoglycan may represent retained bacterial material, but persistent Borrelia burgdorferi infection as a continuing source of peptidoglycan has not been excluded. These studies were not designed to distinguish between those possibilities.
Can Lyme arthritis resemble rheumatoid arthritis?
Yes. Lyme arthritis and rheumatoid arthritis can both cause joint swelling and inflammation, but they are distinct conditions. Lyme arthritis often affects one or a few large joints, particularly the knee, while rheumatoid arthritis more commonly causes a symmetric pattern involving multiple joints.
Clinical Takeaway
The combination of peptidoglycan and NapA could provide targets for future preventive, diagnostic, and therapeutic development. These findings improve our understanding of how bacterial components may contribute to persistent inflammation in Lyme arthritis.
The studies do not determine whether peptidoglycan remains after bacterial clearance or is continually released by persistent organisms. Retained bacterial material, persistent infection, immune dysregulation, or a combination of mechanisms may contribute to ongoing arthritis in individual patients.
Further research is needed to determine why peptidoglycan persists and how it may drive inflammation in Lyme arthritis.
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References
- Jutras BL, Lochhead RB, Kloos ZA, et al. Borrelia burgdorferi peptidoglycan is a persistent antigen in patients with Lyme arthritis. Proceedings of the National Academy of Sciences. 2019;116(27):13498-13507.
- Davis MM, Brock AM, DeHart TG, et al. The peptidoglycan-associated protein NapA plays an important role in the envelope integrity and in the pathogenesis of the Lyme disease spirochete. PLOS Pathogens. 2021;17(5):e1009546.
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
Thank you Virginia Tech and the Justice lab….this gives me hope as I sit her wondering how to get through this day of pain……Our lives are a miserable existence of pain that we plow through like a hero. I will call the lab today to thank them for their very important work. Thanks Dr. Cameron.. I saw “The Red Ring ” twice on the weekend. Very powerful!!!!!! “I have contacted several of our White House politicians to tell them about it..”The children are suffering” 3 times at the end makes you cry!!!!!!