A team of scientists has zeroed in on an enzyme that could revolutionize Lyme disease treatment.
By uncovering the crucial role of BbLDH in bacterial survival and infectivity, they’ve opened the door to highly targeted therapeutics. Their findings even hint at broader applications for fighting other tick-borne diseases.
A Promising New Target for Lyme Disease Treatment
Scientists have identified an enzyme that could be a promising target for developing new treatments for Lyme disease, and potentially other tick-borne illnesses. Their findings, published today (March 20) in mBio, a journal of the American Society for Microbiology, could open the door to more effective therapies.
Lyme disease is the most common tick-borne infection in the United States and Europe. It is caused by the bacterium Borrelia burgdorferi, which has evolved unique metabolic pathways to survive in its environment. Some of these pathways make ideal targets for drug development.
A Surprising Metabolic Pathway
Previous research from Virginia Commonwealth University revealed that B. burgdorferi does not rely on thiamin, an essential cofactor for most organisms. Instead, it depends on the enzyme lactate dehydrogenase (BbLDH) to convert pyruvate to lactate, a process crucial for maintaining its NADH/NAD+ balance. This metabolic adaptation has not been observed in any other microorganism and plays a vital role in the bacterium’s survival.
In this new study, researchers explored the function of BbLDH in B. burgdorferi and its potential as a therapeutic target. Using genetic, biochemical, and structural analysis, including X-ray crystallography, they identified BbLDH’s essential role in the bacterium’s growth and ability to infect a host. Loss-of-function studies confirmed that BbLDH is necessary for the bacterium to thrive both in lab cultures and in living organisms. Additionally, the team performed high-throughput screening and discovered several promising LDH inhibitors that could serve as the basis for future treatments.
A Breakthrough in Lyme Disease Therapeutics
“We discovered that BbLDH has a unique biochemical and structural feature and it is essential for B. burgdorferi growth and infectivity,” said corresponding study author Chunhao (Chris) Li, M.S., M.D., Edward Myers Endowed Professor, the Philips Research Institute for Oral Health, School of Dentistry, Virginia Commonwealth University. “BbLDH can serve as an ideal target for developing genus-specific inhibitors that can be potentially used to treat and prevent Lyme disease.”
The impact of Lyme disease on public health fuels an emerging demand for novel therapeutics to treat Lyme disease. “This report also sheds new light into understanding the role of LDH in the pathophysiology of other tick-borne pathogens,” Li said.
Reference: “Lactate dehydrogenase is the Achilles’ heel of Lyme disease bacterium Borreliella burgdorferi” by Ching Wooen Sze, Michael J. Lynch, Kai Zhang, David B. Neau, Steven E. Ealick, Brian R. Crane and Chunhao Li, 20 March 2025, mBio.
DOI: 10.1128/mbio.03728-24
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