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 ΒιΆΉΣ³»΄«Γ½ 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: βstarveβ 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 ΒιΆΉΣ³»΄«Γ½βs 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. Jewettβs 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 nationβs most common vector-borne diseases. Her team includes a ΒιΆΉΣ³»΄«Γ½ 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 donβt 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
ΒιΆΉΣ³»΄«Γ½ researchers are focused on how B. burgdorferi manages to survive and thrive as it spreads in ticks and mammals to humans.
βThe bacteria need to adapt to two different environments, and so we want to know how it does that,β Jewett says. βWeβre looking at what the bacteria eat and what it needs to survive. In our lab, we call Borrelia a wimpy pathogen because it canβt make a lot of the nutrients it needs on its own, and so it scavenges what it needs from wherever it is.β
The first iteration of the NIH grant allowed the scientists to screen all of the bacteriaβs 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.
“One of these three genes we found is important to the ability of the bacteria to consume riboflavin. We want to target this gene and see if we can starve the bacteria.” β Mollie Jewett, ΒιΆΉΣ³»΄«Γ½ infectious disease expert
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.
βOne of these three genes we found is important to the ability of the bacteria to consume riboflavin,β Jewett says. βWe 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.β
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 that patients donβt have to take general antibiotics that can also harm the bodyβs good bacteria and increase risks for antibiotic-resistant bacteria.
The ΒιΆΉΣ³»΄«Γ½ 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 β25MS 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 sheβs looking forward to growing as a researcher in this next phase.
βAs a first author, I took more ownership over the experiments and the writing process,β Schulz says. β[Jewett] was really great about letting me lead the project as a student. Borrelia is so unique, and thereβs still so much we donβt know, and thatβs what keeps me engaged with this research.β
“… I couldnβt treat it until years after I got infected. So, I truly care about finding new treatments for Lyme disease.” β Grace Easterling, ΒιΆΉΣ³»΄«Γ½ biomedical sciences student
Third-year biomedical sciences undergraduate Grace Easterling says she was drawn to Jewettβs lab because she previously developed Lyme disease and suffered tremendous joint pain. She was determined to find a way to protect others.
βIt was something that, because we live in Florida, wasnβt caught early because itβs not as common,β Easterling says. βI struggled for a long time to get diagnosed, and I couldnβt treat it until years after I got infected. So, I truly care about finding new treatments for Lyme disease and understanding the bacteria.β
Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number R01AI099094. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
