Researchers at Virginia Commonwealth University (VCU) have identified a promising new target for Lyme disease treatment, offering hope for better therapies in the future. The enzyme lactate dehydrogenase (BbLDH) plays a crucial role in the survival and infectivity of Borrelia burgdorferi, the bacteria responsible for Lyme disease.
This discovery could lead to the development of more effective treatments to combat this common tick-borne illness. The findings were published in the journal mBio, from the American Society of Microbiology.
What Is Lyme Disease?
Lyme disease, caused by the bacterium Borrelia burgdorferi, is the most common tick-borne illness in the U.S. and Europe. It affects hundreds of thousands of people each year, often leading to symptoms like fever, headache, and fatigue. If left untreated, the disease can cause long-term complications, such as joint pain and neurological issues.
One of the major challenges in treating Lyme disease is the bacterium’s ability to adapt and survive in both the tick and mammalian hosts. B. burgdorferi uses a unique metabolic pathway to maintain its survival, which relies on the enzyme BbLDH. Researchers at VCU have now identified this enzyme as a potential target for new treatments.
The Role of BbLDH in B. burgdorferi Survival
Chunhao (Chris) Li, MD, of VCU’s School of Dentistry, led the study and explained the importance of BbLDH. “We discovered that BbLDH has a unique biochemical and structural feature, and it is essential for B. burgdorferi growth and infectivity,” said Dr. Li. “BbLDH can serve as an ideal target for developing genus-specific inhibitors that could potentially treat and prevent Lyme disease.”
The enzyme BbLDH is vital for the bacterium’s ability to convert pyruvate to lactate, maintaining an internal balance of NADH/NAD+ ratios that are critical for energy production and protecting the bacteria from oxidative stress. This unique metabolic pathway is a key factor in the survival of B. burgdorferi in its host.
How the Researchers Made the Discovery
To explore the potential of BbLDH as a therapeutic target, the VCU team combined several scientific methods. They used genetics, biochemistry, and crystallography to examine the enzyme’s structure. Additionally, loss-of-function studies showed that BbLDH is essential for the bacteria’s ability to grow in lab settings and infect a host in vivo.
“This discovery highlights the crucial role that BbLDH plays in the survival of the bacterium,” said Dr. Li. “Targeting this enzyme could significantly disrupt the pathogen’s ability to infect and grow.”
Potential for New Lyme Disease Treatments
To further investigate the therapeutic potential of BbLDH, the researchers conducted a high-throughput screening of chemical compounds. They identified four potential inhibitors of the enzyme, two of which showed promising results. Methoxsalen and medicarpin were both found to reduce the growth of B. burgdorferi in laboratory tests.
Methoxsalen, a compound previously studied in combination with ultraviolet light therapy for treating vitiligo, and medicarpin, a naturally occurring compound with anti-inflammatory and antimicrobial properties, have both demonstrated effectiveness in inhibiting BbLDH. While these compounds have been studied for other purposes, their potential to treat Lyme disease is now being explored.
Next Steps for Research and Development
The VCU researchers plan to continue refining these inhibitors to improve their efficacy and explore their potential for clinical use. “We are optimistic that these inhibitors could form the basis for new therapies to combat Lyme disease,” said Dr. Li. “We also plan to investigate their potential use in combination with other treatments to improve outcomes for patients.”
The research team is also exploring the possibility of using these inhibitors to treat other tick-borne diseases. As Lyme disease is just one of many illnesses caused by ticks, this new discovery could have a broad impact on public health.
The Future of Lyme Disease Treatment
As the search for effective treatments for Lyme disease continues, the identification of BbLDH as a therapeutic target brings new hope. If these inhibitors can be further developed and tested, they may provide a valuable tool in the fight against this widespread illness.
