Lyme disease, a debilitating illness triggered by a subtle tick bite, inflicts severe pain and inflammation on nearly half a million Americans each year. Current medical interventions primarily focus on treating established infections with antibiotics. However, Dr. Mollie Jewett, an infectious disease expert at the University of Central Florida (UCF), is pioneering a novel strategy: disrupting the Borrelia burgdorferi bacteria's ability to thrive by depriving it of crucial nutrients before it can disseminate throughout the body.

Dr. Jewett, who leads the Immunity and Pathogenesis Research Division at UCF's College of Medicine, has secured a significant .5 million grant from the National Institutes of Health, marking her third consecutive federally funded research cycle. Her work builds on over a decade of research into targeting vulnerabilities in B. burgdorferi, the pathogen responsible for Lyme disease. This research has particularly benefited from the personal insights of a UCF undergraduate team member who, having previously suffered from the disease's severe pain, contributes a unique perspective to the study.

Targeting Nutritional Pathways in Borrelia

The research team at UCF is diligently investigating the metabolic mechanisms that enable Borrelia burgdorferi to adapt and flourish across distinct environments, specifically within ticks and subsequently in mammals, including humans. Dr. Jewett emphasizes the bacteria's inherent limitations, describing it as a “wimpy pathogen” due to its inability to synthesize many essential nutrients independently. Instead, it scavenges necessary resources from its host environment. This critical dependency on external nutrient sources presents a promising target for therapeutic intervention, as understanding its nutritional requirements is key to disrupting its lifecycle.

Initial phases of the NIH grant allowed researchers to systematically screen the bacteria’s entire genetic makeup to pinpoint genes crucial for infection. Subsequent research narrowed this focus to three specific genes that appeared instrumental in the bacteria's spread from the initial bite site to other bodily systems. A breakthrough discovery highlighted the importance of riboflavin, commonly known as vitamin B2, revealing that Borrelia burgdorferi actively salvages this vitamin from each host to sustain its metabolic processes. This finding has now directed the team’s efforts towards targeting the gene responsible for riboflavin uptake.

Strategic Riboflavin Deprivation as a Therapeutic Approach

The current phase of research specifically targets a gene vital for the bacteria’s riboflavin consumption. The hypothesis is that by inhibiting this gene, researchers can effectively “starve” the bacteria, thereby preventing a successful infection. If this theory proves correct, it could pave the way for highly specific treatments against Borrelia burgdorferi. Such targeted therapies would offer a significant advantage over conventional broad-spectrum antibiotics, which often harm beneficial gut flora and contribute to the rise of antibiotic-resistant strains. This precision approach aims to minimize collateral damage to the patient’s microbiome while effectively combating the Lyme disease pathogen.

Collaboration with scientists from Baylor University is enabling the UCF team to further unravel the precise mechanisms by which Borrelia burgdorferi utilizes riboflavin for its cellular activities and energy generation. This collaborative effort, supported by the invaluable contributions of doctoral and undergraduate students—including one who personally experienced the severe joint pain of Lyme disease—underscores the dedication to finding innovative solutions. The personal connection to the disease among team members amplifies the drive to develop effective new treatments and deepen the understanding of this complex bacterial infection, ultimately aiming to protect others from its debilitating effects.