Chronic pain associated with Lyme disease has confounded scientists for many years. Patients will often complain of joint pain even long after the infection from the offending spirochete—Borrelia burgdorferi—has been cleared. Now, investigators at Virginia Tech believe they have discovered one of the molecules shed by the microbes that mediate the host inflammatory response. Findings from the new study—just published in PNAS through an article entitled “Borrelia burgdorferi peptidoglycan is a persistent antigen in patients with Lyme arthritis”—could help pave the way for novel therapeutics to relieve many patients of the joint paint associated with Lyme disease.
“This discovery will help researchers improve diagnostic tests and may lead to new treatment options for patients suffering from Lyme arthritis,” explained lead study investigator Brandon Jutras, PhD, assistant professor of biochemistry at Virginia Tech. “This is an important finding, and we think that it has major implications for many manifestations of Lyme disease, not just Lyme arthritis.”
Reported incidences of Lyme disease, the most reported vector-borne disease in the country, have increased by more than 6,000% in the past 15 years in the state of Virginia. The Centers for Disease Control estimates that approximately 300,000 people are diagnosed with Lyme disease annually in the United States. Scientists predict that the number of people who become infected with Lyme will increase as our climate continues to change.
Amazingly, this research may provide a new way to diagnose Lyme disease and Lyme arthritis for patients with vague symptoms based on the presence of the cellular component called peptidoglycan in synovial fluid.
The research team found Borrelia peptidoglycan is a major contributor to Lyme arthritis in late-stage Lyme disease patients. Peptidoglycan is an essential component of bacterial cell walls. All bacteria have some form of peptidoglycan, but the form found Borrelia burgdorferi has a unique chemical structure. Moreover, when the bacteria multiply, they shed peptidoglycan into the extracellular environment, because its genome does not have the appropriate proteins to recycle it back into the cell.
“We can actually detect peptidoglycan in the synovial fluid of the affected, inflamed joints of patients that have all the symptoms of Lyme arthritis but no longer have an obvious, active infection,” Jutras said.
Peptidoglycan elicits an inflammatory response and the molecule persists in the synovial fluid, which means that our bodies continue to respond, without mounting a counter-response.
The next phase of work by the research team is to use methods to destroy the peptidoglycan or intervene to prevent a response, which could get rid of Lyme disease symptoms. Jutras predicts that with either therapy patients would start recovering sooner.
Clinical samples included in this study were obtained from patients that had confirmed cases of Lyme disease under the guidelines of the CDC, but virtually all did not respond to oral and/or intravenous antibiotic treatment. The presence of peptidoglycan in these patients’ synovial fluids may explain why some people experience symptoms of late-stage Lyme disease in the absence of an obvious infection. In this case, the usual antibiotic treatments for Lyme disease would no longer be helpful, but this discovery might provide avenues for new treatments.
Members of the Jacobs-Wagner lab purified the peptidoglycan and removed all other bacterial components and asked: Is peptidoglycan all on its own capable of causing arthritis in a mouse model? Within 24 hours post-injection, mice presented with dramatic joint inflammation, indicating that peptidoglycan can cause arthritis.
“We are interested in understanding everything associated with how patients respond, how we can prevent that response, and how we could possibly intervene with blocking therapies or therapies that eliminate the molecule entirely,” Jutras concluded.