Epidemic. Pandemic. These terms have become second nature to us, popping up in everyday conversations, and for good reason – COVID-19 is the latest pandemic to pose a threat to humanity.
But in recent months, much less attention has been paid to another widespread problem that has proliferated since the late 1970s: Lyme disease.
Lyme disease is the most reported vector-borne disease in the country. Over the past 20 years, the United States has seen a dramatic increase in the number of reported cases and the geographic distribution of the disease. In Virginia, the disease is transmitted by blacklegged ticks, which are infected with the bacteria Borrelia burgdorferi, which causes Lyme disease.
Virginia Tech’s Assistant Professor Brandon Jutras and his lab have continued to fight the Lyme disease outbreak over the past year, and they recently identified another missing piece of the Lyme disease puzzle.
“This discovery allows us to better understand how Borrelia burgdorferi causes inflammation and disease,” said Mari Davis, lead author of the paper, a former masters graduate of the Jutras Lab in the Department of Biochemistry at the College of Agriculture and Life Sciences. . “It’s a testament to how uniquely this bacteria is – and how we need to keep working to better understand what’s going on behind the scenes in order to develop future diagnoses and treatments.”
Their results were recently published in PLOS pathogens, an open access, peer-reviewed medical journal.
Almost all bacteria, including the bacteria that causes Lyme disease, make a net-like bag to protect the inside of their cells. This bag is known as a peptidoglycan. In 2019, Jutras identified peptidoglycan, a persistent component of the cell wall of the bacteria Borrelia burgdorferi, as a likely culprit for inflammation and Lyme arthritis, the most common symptom of Lyme disease in stage advanced.
Previous research by Jutras has shown that peptidoglycan from Borrelia burgdorferi persists in the body of Lyme arthritis patients after the bacteria enter the body. Weeks to several months after the initial infection, the peptidoglycan remains, causing inflammation and pain.
In this latest development, the lab discovered a protein associated with the peptidoglycan of Borrelia burgdorferi that plays an amplifying role in inflammation in patients with Lyme arthritis by acting as a molecular beacon that antagonizes patients’ immune systems.
Using an unbiased proteomic approach and the Fralin Life Sciences Institute’s Core Services Mass Spectrometry Research Incubator (VT-MSI), the team identified the protein as NapA. NapA, which stands for Neutrophil Attracting Protein A, is a remarkable immunomodulatory molecule that is able to recruit immune cells, called neutrophils, to the inflammatory peptidoglycan.
“We are delighted with the discovery, publication and implications of Dr. Jutras’ NapA for the diagnosis and treatment of Lyme disease. His research fits perfectly with our institute’s vision of making an impact on society by taking a problem-centric approach to tackling the environment and the life sciences. global challenges, ”said Matt Hulver, executive director of the Fralin Life Sciences Institute.
“NapA is another piece of an ever-changing puzzle; it appears to play a fundamental role in daily bacterial life by contributing to the overall protective properties of peptidoglycan, but it comes across as a sneaky protein capable of fooling our immune system. said Jutras, a faculty affiliated with the Fralin Life Sciences Institute and the Center for Emerging, Zoonotic, and Arthropod-Borne Pathogens.
“We believe that the sneaky side of NapA has two modes: at the onset of infection, when bacteria die and release NapA and peptidoglycan, it acts as a decoy to attract immune cells, which allows viable bacteria to enter. escape and cause disease. In later stages of the disease, it can work to attract immune cells to peptidoglycan, a molecule capable of causing inflammation and arthritis, ”Jutras said.
To determine how NapA attracted neutrophils, Davis looked for Caroline Jones, who was an assistant professor in the Department of Biological Sciences at Virginia Tech College of Science at the time of the discovery. His laboratory specializes in the study of the chemoattraction of neutrophils. Jones placed neutrophils in the middle of a microfluidic chip, which acts like a labyrinth in which cells can wander. On one side of the chip there was pure peptidoglycan, on the other there was peptidoglycan with NapA.
The Jones and Jutras labs have shown that neutrophils migrate rapidly to the side with NapA, proving that the protein is able to give off chemical signals that attract neutrophils in its direction and the peptidoglycan.
With this new piece of the puzzle in hand, Jutras plans to complement the lab’s current efforts to improve diagnostic testing and treatment for Lyme disease.
“From a prevention and diagnostic perspective, it is possible that the combination of peptidoglycan and NapA is a new target for diagnosis,” Jutras said. “This could, in theory, also be a possible avenue for vaccine development. These are global possibilities that we are actively seeking. One thing we do know for sure is that this discovery gives us a better understanding of how peptidoglycan can lead to a patient with Lyme arthritis. symptology. “