There's a virus within a bacterium within a parasite, and University of Kentucky researchers are figuring out how to make them kill each other.
Brian Stevenson, Ph.D., a professor in the College of Medicine's Department of Microbiology, Immunology and Molecular Genetics and the Martin-Gatton College of Agriculture, Food and Environment's Department of Entomology, is leading two separate but related studies aimed at fighting Lyme disease by turning the bacteria's own internal systems against itself.
Now entering his 28th year at UK, Stevenson has secured funding from both the National Institutes of Health (NIH) and the Global Lyme Alliance (GLA) to explore these novel pathways. The dual research approach addresses both the fundamental biology and the potential for new treatments for what Stevenson calls a homegrown problem in Kentucky.
It's not your imagination
Recent data shows a significant spike in local prevalence. According to research from the Kentucky Department for Public Health (KDPH), reported tick-borne diseases increased by 128% between 2020 and '23. Most notably, cases of Lyme disease skyrocketed by approximately 275% during that same three-year period. Kentucky now ranks among the top 25 U.S. states with the highest risk for tick-borne illness.
"Lyme disease is here in Kentucky. This is something that is real," Stevenson said.
The UK Department of Entomology and the KDPH have been closely monitoring this expansion through a multi-year surveillance program. Although the lone star tick (the culprit behind Alpha-gal syndrome) remains the most common species in the state, the blacklegged tick (the vector for Lyme disease) is now established throughout the Commonwealth. Experts attribute this spread to ticks migrating from the Northeast and upper Midwest into Kentucky, finding an ideal environment in the state's vegetation and high humidity.
As spring temperatures climb, tick activity across the state typically surges. While many species remain dormant during the coldest months, the blacklegged tick can be active year-round. However, it is most dangerous to humans during the spring, summer and fall.
As of 2024, surveillance teams confirmed established blacklegged tick populations in at least 19 Kentucky counties. And in those increased populations, the incidence of prevalence of Lyme disease is high: In a recent field survey of 160 blacklegged ticks, 40 tested positive for the bacteria that causes Lyme disease.
These factors make Stevenson's research especially important to the Bluegrass.
Phage wisdom
The two grants support distinct yet complementary goals to better understand and treat the disease, which affects approximately 500,000 people in the U.S. every year.
The NIH study investigates how the bacteria and its internal viruses, known as bacteriophages, normally control each other. Researchers are looking for the specific signaling pathways the bacteria use to keep the bacteriophages in check and control when they will be produced.
The GLA supports an applied study aimed to create a variant bacteriophage with no internal controls. This engineered virus would be designed to immediately replicate and destroy Lyme bacteria upon infection, offering a potential new form of phage therapy.
The research centers on the symbiotic relationship between Lyme bacteria and the bacteriophages they carry. Normally, these viruses provide an infectious advantage to the bacteria. Stevenson's lab aims to identify a druggable target within this relationship to hijack their communication.
"We're basically trying to figure out how to hijack the communication systems to make the disease kill itself," Stevenson said.
This method could provide a vital alternative to broad-spectrum antibiotics like doxycycline, which kill off beneficial bacteria in addition to the Lyme agent. Furthermore, these new therapies could be effective during late-stage infections, when the bacteria often "hunker down" in parts of the body that are difficult for the immune system to reach.
Applications
When asked about the implications for alpha-gal, another well-known illness in the region, Stevenson clarified that the two are completely unrelated in every way except for ticks being the perpetrator. While Lyme is a bacterial infection, alpha-gal syndrome is an allergy that can develop after a bite from a Lone Star tick. Stevenson noted that the mechanisms for developing the allergy are entirely different from the bacterial signaling he is studying.
Though not applicable to alpha-gal, the impact of this work may extend beyond Lyme disease. Several years ago, the Stevenson lab discovered a regulatory protein in the bacteria, named BpuR (pronounced "beeper"), that has a human version. This human protein is associated with the replication of HIV and genetic conditions such as Fragile X syndrome.
"These kinds of studies often have results that you didn't anticipate," Stevenson said. "We thought we were studying regulation in the Lyme Borrelia bacteria, and then to discover something that, well, humans use it also."
Stevenson wanted to emphasize that leading-edge research like this is happening across campus, and that breakthroughs in the laboratory can lead to better lives throughout the world.
"There's a lot of cool science going on at UK," Stevenson said. "Things that are impacting human health."
And it can begin with something as small as a tick.
This research was supported by the Global Lyme Alliance (GLA). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Kentucky Science and Technology Corporation.
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 R21AI197062-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
