Virginia Tech researchers have discovered a protein that plays an amplifying role in causing inflammation in Lyme arthritis patients by acting as a molecular beacon that antagonizes the patients' immune system.
In 2019, Bradon Jutras, senior author on a PLOS Pathogens paper published today, identified peptidoglycan, a lingering cell wall component of the bacterium Borrelia burgdorferi, as a likely cause of Lyme-related inflammation and Lyme arthritis. His previous research also showed that peptidoglycan in Borrelia burgdorferi lingers in the bodies of Lyme arthritis patients after the bacteria has entered the body. Weeks to months after the initial infection, the peptidoglycan remains, inciting inflammation and pain.
The protein that was discovered is associated with the peptidoglycan. It was discovered using an unbiased proteomics approach and named NapA, which stands for neutrophil attracting protein A. NapA is an immunomodulatory molecule that is able to recruit neutrophils toward the inflammatory peptidoglycan.
"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, but it moonlights as a devious protein capable of tricking our immune system," said Jutras.
"We believe NapA's devious side has two modes: 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. In later stages of disease, it may act to attract immune cells to peptidoglycan, a molecule capable of causing inflammation and arthritis," Jutras said.
"From a prevention and diagnostic perspective, it's possible that the combination of peptidoglycan and NapA could be a novel target for diagnostics," Jutras said. "It could, in theory, be a possible avenue of vaccine development as well. These are big picture possibilities that we are actively pursuing. One thing that we know for sure is that this finding furthers our understanding of how peptidoglycan can drive Lyme arthritis patient symptomatology."