Imagine enjoying a quiet hike through a forest trail, a walk through the park, or even a stroll on the beach. A few days later, you notice a strange red rash, maybe shaped like a bull’s-eye, and soon you’re feeling tired, achy, and feverish. These could be the first signs of Lyme disease, the most common tick-borne illness in the United States.

What Is Lyme Disease?

Lyme disease is caused by a bacterium called Borrelia burgdorferi, which spreads through the bite of infected black-legged ticks (also called deer ticks). These tiny ticks, often no bigger than a poppy see, can easily go unnoticed. If they stay attached for at least 24 to 48 hours, they can transmit the bacteria into the body.

Early signs of Lyme disease include fever, fatigue, muscle and joint aches, headache, and the hallmark erythema migrans, or bullseye, rash. If left untreated, the infection can spread to the joints, nervous system, and even the heart. Most people recover with antibiotics, typically doxycyclin, but not everyone.

A Growing Threat

Lyme disease is no longer limited to rural or forested areas in the Northeast. It’s spreading. The Centers for Disease Control and Prevention (CDC) estimates that nearly 476,000 people in the U.S. are diagnosed and treated for Lyme disease each year.

Why the increase?

One major reason is climate change. As temperatures rise and seasons shift, black-legged ticks are expanding their range into new regions, including parts of the Midwest, South, and Canada. Warmer winters and longer summers allow ticks to survive and stay active for more of the year. This means more people and pets are at risk in areas that weren’t historically affected.

Urban development also plays a role. As forests are fragmented by housing and roads, people are living closer to tick habitats, increasing the chances of exposure.

When Lyme Disease Doesn’t Go Away

While most people recover after treatment, about 10–20% of patients continue to have symptoms like joint pain, fatigue, and brain fog. This is known as Post-Treatment Lyme Disease Syndrome (PTLDS), and for years, its cause has been unclear.

A 2025 study by McClune et al. may offer an answer. Researchers found that fragments of the Lyme bacterium's cell wall, specifically peptidoglycan, can remain in the body even after the bacteria itself is gone. These fragments were found in the liver and joints of mice, and in the joint fluid of people with Lyme arthritis. They can trigger ongoing immune reactions, which might explain lingering symptoms. This discovery could be the key to developing treatments that address PTLDS more effectively.

A Promising New Antibiotic

At the same time, scientists are working to improve Lyme treatment itself. In another 2025 study, Gabby et al. screened nearly 500 existing FDA-approved drugs to see if any might work better than current options. One drug stood out: piperacillin, a type of beta-lactam antibiotic.

In lab tests and mouse models, piperacillin:

• Killed Lyme bacteria at 100 times lower doses than doxycycline
• Did not harm beneficial gut bacteria, unlike doxycycline
• Reduced joint inflammation and improved recovery
• Appeared highly specific to B. burgdorferi, with minimal effects on other microbes

Most importantly, piperacillin was just as effective as doxycycline in clearing infection in mice, but caused far less disruption to the microbiome, a key concern with broad-spectrum antibiotics.

Protecting the microbiome during Lyme disease treatment is important because this community of beneficial bacteria plays a critical role in your overall health. A healthy microbiome supports your immune system, helps with digestion, and prevents harmful bacteria from taking over. When broad-spectrum antibiotics like doxycycline are used, they can disrupt this balance by killing off not only the harmful bacteria but also the good ones. This disruption can lead to side effects like digestive problems, weakened immunity, and even serious infections like C. difficile. It may also contribute to long-term issues such as increased inflammation, allergies, or mental health concerns. That’s why the discovery that piperacillin, an existing antibiotic, can effectively treat Lyme disease in mice without harming the microbiome is so significant. By preserving the body’s natural defenses while still clearing the infection, piperacillin could offer a safer, more targeted treatment option for patients.

What You Can Do

As Lyme disease spreads, awareness and prevention are more important than ever. Here are steps you can take:

• Wear long sleeves and pants in wooded or grassy areas
• Use EPA-approved insect repellent (like DEET or picaridin)
• Check your body and clothing for ticks after spending time outdoors
• Shower within two hours of being outdoors to help wash off ticks
• Remove ticks promptly with tweezers—slow, steady pulling is key

If you develop a rash or feel unwell after a possible tick bite, seek medical care right away. Early treatment makes a big difference.

The Road Ahead

Lyme disease is complex, and it’s becoming more common as our environment changes. But thanks to recent research, we are closer than ever to understanding why some people stay sick and how to treat the disease more safely and effectively. New discoveries like piperacillin and the immune-triggering role of peptidoglycan are giving hope to those affected by this growing health challenge.

1. Gabby ME, Bandara A, Outrata LM, et al. A high-resolution screen identifies a preexisting beta-lactam that specifically treats Lyme disease in mice. Sci Transl Med. Published online 2025.
2. McClune ME, Ebohon O, Dressler JM, et al. The peptidoglycan of Borrelia burgdorferi can persist in discrete tissues and cause systemic responses consistent with chronic illness. Sci Transl Med. Published online 2025.