Triggered by a near painless tick bite, Lyme disease causes severe pain and inflammation for more than 475,000 people in the U.S annually, according to the Centers for Disease Control.

Medicine can treat infections after people get sick, but University of Central Florida infectious disease expert Mollie Jewett is seeking to halt Borrelia burgdorferi bacteria, which causes Lyme disease, in its tracks without relying on general antibiotics. Her goal: "starve" the bacteria of the nutrients they need to function before they spread through the human body.

Jewett, professor and head of the Immunity and Pathogenesis Research Division at UCF's College of Medicine, is supported by a recently renewed five-year, $2.5 million grant from the National Institutes of Health.

She is entering a third consecutive federally funded research cycle with $513,314 received this year. Jewett's research builds upon more than a decade of discoveries that have narrowed the search for ways to stop B. burgdorferi from triggering Lyme disease, one of the nation's most common vector-borne diseases. Her team includes a UCF undergraduate who occasionally struggled to walk because of pain from Lyme disease.

The disease is spread by blacklegged ticks that become infected after biting mammals or birds carrying the bacteria. The ticks are so small, humans often don't notice they have been bitten. Symptoms include fever, chills, headache and fatigue, which often are misdiagnosed as a virus or the flu. Even after treatment, Lyme disease patients can face complications including nervous system and heart issues, severe fatigue and arthritic pain.

The disease is most commonly found in Maine to Virginia and in the upper Midwest but is spreading as suburban growth enters wildlife areas. Florida reports few cases of Lyme disease annually, but travelers who go to endemic areas like New England are at increased risk.

A new approach to battle Borrelia

UCF researchers are focused on how B. burgdorferi manages to survive and thrive as it spreads in ticks and mammals to humans. 

The bacteria need to adapt to two different environments, and so we want to know how it does that. We're looking at what does the bacteria eat and what does it needs to survive. In our lab, we call Borrelia a wimpy pathogen because it can't make a lot of the nutrients it needs on its own and so it scavenges what it needs from wherever it is."

Mollie Jewett, professor and head of the Immunity and Pathogenesis Research Division, UCF's College of Medicine

The first iteration of the NIH grant allowed the scientists to screen all of the bacteria's genes that might be important for the infection. With the second grant, Jewett targeted three genes that appeared to play a role in spreading the infection from a bite on the skin to other parts of the human body.

Now they have focused on riboflavin, commonly known as vitamin B2, after discovering that B. burgdorferi salvages the vitamin from each host to sustain itself.

"One of these three genes we found is important to the ability of the bacteria to consume riboflavin," Jewett says. "We know that riboflavin is a precursor for other cellular activities that are important to the metabolism of the bacteria. Essentially, we want to target this gene and see if we can starve the bacteria."

If their theory is successful, it could lead to therapies specific to B. burgdorferi that would prevent successful bacterial infection by limiting its riboflavin uptake. An advantage of such potential treatments would be patients don't have to take general antibiotics that can also harm the body's good bacteria and increase risks for antibiotic-resistant bacteria. 

The UCF team is collaborating with Baylor University scientists to trace exactly how riboflavin is used by the bacteria.

Students driving discovery

Biomedical sciences doctoral student Anna Schulz played a key role in pinpointing specific ways the bacteria use riboflavin to generate energy. She served as first author on a recent publication examining these processes, and says she's looking forward to growing as a researcher in this next phase.

"As a first author, I took more ownership over the experiments and the writing process," Schulz says. "[Jewett] was really great about letting me lead the project as a student. Borrelia is so unique and there's still so much we don't know, and that's what keeps me engaged with this research."

Third-year biomedical sciences undergraduate Grace Easterling says she was drawn to Jewett's lab because she previously developed Lyme disease and suffered tremendous joint pain. She was determined to find a way to protect others.

"It was something that, because we live in Florida, wasn't caught early because it's not as common," Easterling says. "I struggled for a long time to get diagnosed, and I couldn't treat it until years after I got infected. So, I truly care about finding new treatments for Lyme disease and understanding the bacteria."