How to fight Lyme may lie in the biology of its disease-causing bacteria

Not all cell walls are created equal. Take the peculiar makeup of the Borrelia burgdorferi bacterium’s cell wall. It might play a role in lingering symptoms of Lyme disease — the most common tick-borne infection in the United States. That makeup might also be key to developing new treatments for the disease, researchers report in two studies published April 23 in Science Translational Medicine.

Somewhere between 90,000 and nearly 500,000 people are diagnosed and treated for Lyme disease each year in the United States. About 15 percent of those people continue to experience symptoms including fatigue, body aches and memory problems even after the acute phase of the disease is treated — a condition called Post Treatment Lyme Disease Syndrome, or PTLDS. However scientists aren’t sure what causes the lingering symptoms of PTLDS once antibiotics have killed the living bacteria inside the body.

In a previous study, microbiologist Brandon Jutras found that patients with post-infectious Lyme arthritis, a late-stage form of Lyme disease, still have bacterial cell wall fragments called peptidoglycans in the fluid between their joints, even after treatment. This mesh-like skeleton is made of sugars and amino acids, seldom-seen components that can influence the responses of the body’s immune system. Experiments had also shown differences in the amino acids and sugars making up B. burgdorferi’s peptidoglycans compared with other bacteria.

“That was kind of the impetus of the study, to figure out if the chemical components of the peptidoglycan were important in the persistence” of the disease, says Jutras of Northwestern University’s Feinberg School of Medicine in Chicago.

In one of the new studies, Jutras and his colleagues found that in mice with Lyme arthritis, B. burgdorferi’s peptidoglycan fragments accumulated in the liver where they can linger for weeks or months.

“Something is being left behind that is continuing to elicit an immune response,” says study coauthor Mecaila McClune, a biochemist also at Northwestern.

This immune response is similar to what is seen in patients with long COVID, the researchers wrote, which may also be triggered by viral fragments left behind after the main infection is gone.

In the second paper, the team reports the effects of an antibiotic that interferes with the peptidoglycan as the cell is trying to divide and replicate, meaning it can stop a new infection in its tracks.

The antibiotic is piperacillin, a relative of penicillin, and a low dose of it effectively treats Lyme disease caused by B. burgdorferi in mice. Jutras says his team screened approximately 500 molecules to find one that could stop the growth of the bacterium — “and piperacillin did just that.”

A new treatment for Lyme disease is important because the current gold standard treatment, doxycycline, fails in 10 to 20 percent of cases and can have harsh side effects on the gut microbiome.

Jutras hopes that one day piperacillin, which is already approved by the U.S. Food and Drug Administration for human use in infections such as pneumonia, can be given to people at their primary care doctor’s office as a preventive against Lyme disease. “We’re really excited about the idea of using this directly after a tick bite for high-risk people,” he says.

But unlike doxycycline, which is a pill, piperacillin is delivered via injection. This might make piperacillin less useful, since many patients avoid taking shots, says Justin Radolf, a pediatrician at UConn Health in Farmington who was not involved in the research.

Still, the research used innovative technologies to highlight important and previously poorly understood parts of the bacterium’s biology, Radolf says. “People now are beginning to realize that understanding Lyme disease requires that we really understand the bacterium and what makes it different from many other bacteria that cause disease.”