Lyme disease, caused by a spiral-shaped bacterium known as Borrelia burgdorferi (Bb), is the cause of more than 90 percent of all arthropod-borne diseases affecting humans in the United States. Arthropods are a group of animals that includes lobsters, crabs, ticks, spiders, mites, insects, centipedes, and millipedes. Estimates from the Centers for Disease Control and Prevention (CDC) suggest that 300,000 people each year are affected by Lyme disease. Total direct medical costs of Lyme disease and post-treatment Lyme disease syndrome (PTLDS) in the United States are estimated at $1.3 billion per year.
“Controlled trials of long-term antibiotic treatment for post-treatment Lyme disease symptoms have failed to show benefits,” said Catherine Brissette, PhD, an assistant professor in the Department of Biomedical Sciences at the University of North Dakota School of Medicine and Health Sciences. “If active infection is not responsible, what causes the persistent, lingering symptoms in patients treated with long-term antibiotics? Our data suggest Bb is a ‘hit and run’ pathogen, and the presence of live bacteria is not required to drive persistent inflammation.”
Inflammation is the human body’s immunological defense against invasion by foreign organisms, such as bacteria and viruses. It is marked by redness, heat, swelling, pain, and loss of function of a body part.
The National Institutes of Health has granted Brissette over $380,000 to pursue a unique approach to fend off the effects of Lyme disease. Her work will look at how exposure to Bb leads the DNA (deoxyribonucleic acid) in cells to code for chronic inflammation, which is a hallmark of numerous neurodegenerative and neuroinflammatory diseases.
DNA contains the instructions used by cells to produce proteins, the building blocks of the human body that compose muscle, bone, skin, hair, and every other body part or tissue. The DNA code is communicated to the protein-building mechanisms in cells by RNA (ribonucleic acid).
Brissette and her research team will look at a special type of RNA called microRNA that, instead of communicating DNA code to build proteins, act to silence the process. Previous work by Brissette has shown that certain microRNA increase in cells after exposure to Bb.
“This will be the first study to compare global changes in the microRNA landscape following exposure to Bb,” Brissette said. “In addition to understanding how these microRNAs drive inflammation and disease, our study may uncover novel microRNA biomarkers. MicroRNAs induced in certain disease states can be detected in blood and can have diagnostic and prognostic utility.”
The NIH’s grant to Brissette came through the UND SMHS’s Epigenetics COBRE, (pronounced “KOH-bree”), an acronym for the NIH’s Centers of Biomedical Research Excellence program.
The study of how environmental factors—everything from blood glucose levels to stress—may affect DNA is known as epigenetics (a combination of the prefix epi, derived from Greek for “above,” and the word genetics). Scientists who study epigenetics look at how genes are expressed (how genes are turned on or off) without affecting the DNA sequence directly.
“I am grateful to the UND Epigenetics group, particularly my co-investigator Archana Dhasarathy, PhD, and the COBRE Principal Investigator Roxanne Vaughan, PhD,” said Brissette. “Through my interactions with this dynamic group, I was able to take my research in Lyme disease into a new and exciting area by blending neuroscience, infectious disease and epigenetics. Having strengths in all three of these research areas at UND really allows individual investigators to think outside the box and apply knowledge from other disciplines to their own.”
Other researchers working with Brissette in her study are Timothy Casselli, PhD, a UND postdoctoral researcher, and Derick Thompson, a UND graduate student.
“We hope these studies lead to a broader understanding of how patients remain symptomatic even after antibiotic treatment,” she said. “Once we understand the mechanisms, we can then develop strategies to treat patients suffering from long-term complications. Our studies should also uncover novel biomarkers that we can use to diagnose patients as well as predict disease course and severity. Having this information will allow for faster diagnosis and earlier intervention.”