ECU researchers tackle Lyme disease
BY MICHAEL ABRAMOWITZ
The Daily Reflector
Friday, June 22, 2018
There is nothing for humans to like about ticks, but a Borrelia burgdorferi microbe never met a tick it did not like.
That spells serious trouble for people, and that has East Carolina University researchers scrambling to unlock the genetic secrets of the bacteria that, when transmitted from ticks to humans, can cause the rarely fatal but often debilitating features of Lyme disease.
U.S. health officials suggest that the number of people getting Lyme disease is growing, with as many as 300,000 possible cases reported, racking up $2 billion annually in health care costs. Contributing factors are the intrusion of residential construction into tick habitats and the animals that carry them, according to information from the U.S. Centers for Disease Control and Prevention and National Institutes of Health.
As deer, mice and other wild creatures relocate and seek refuge in other areas, they carry and disperse ticks which then transfer to pets, that bring them home, or directly to humans who brush against leaves and grasses which act as springboards.
An ECU research project funded through a $1.6 million grant from the National Institute of Allergy and Infectious Diseases, part of the NIH, is studying the Borrelia bacteria, particularly its genetic makeup, in hope of intercepting its ability to survive and infect its hosts with Lyme disease.
The project is led by MD Motaleb, a doctoral associate professor in the Department of Microbiology and Immunology at the Brody School of Medicine, and his research team, including postdoctoral researcher Hui Xu, graduate student Priyanka Theophilus and research specialist Zhou Yu.
“I really love studying bacterial genetics,’ he said. “Ticks are a very interesting area of this field, particularly using the mouse model to study Lyme disease. Only a few labs have the ability to do that and we are fortunate to be able to manipulate bacteria to study their transmission to a host.”
Among the several species of ticks, only the Ixodes scapularis, commonly known as the deer tick or black-legged tick, is a vector, or transmitter, of the Borrelia bacteria that causes Lyme disease.
“We don’t know why, but we believe there are some mutual interests; there must be some symbiotic relationship between the two,” Motaleb said.
Once inside a tick that has been engorged by its blood meal — becoming up to 10 times its normal size — most of the thousands of bacteria that enter it die as the blood is digested, possibly because the available nutrient content diminishes. It might be that as the bacteria die, they in turn become nutrition for the tick, but we don’t know for certain.
The Borrelia bacteria have the specific characteristics that cause Lyme disease, and Motaleb and his crew study how they manage to get into ticks.
“The ultimate objective is to learn the factors of the bacteria that produce disease,” he said. “It’s basically a process of elimination, knocking out some molecules and studying their genetic characteristics, particularly their motility, or ability to move through a body.”
There are many thousands of genes in a bacteria, but the researchers focus on finding those genes that relate to the bacteria’s movement functions by use of flagella, whip-like appendages that project the bacteria forward and back. The researchers’ goal is to prevent or interfere with their ability to move. It takes a long time to characterize one gene, and Motaleb’s team has more than 60 to locate and work through.
“If you get Lyme disease, this is swimming through your body, and cause inflammation of tissue, commonly in joints, heart tissue and brain tissue, based on the chemical content of those tissues that attract the bacteria,” Motaleb said.
Not all animals infected with Borrelia develop Lyme disease symptoms. Mice do not, but people and dogs do contract the disease.
Once infected with Lyme, the disease is believed anecdotally to be communicable from one host to another by means of blood and/or fluid transfer, including through sexual contact, Motaleb said. Consequently, the research Motaleb and his team do on Lyme disease can potentially translate into effects on other diseases, such as syphilis and HIV, he said.
Motaleb’s co-researcher, Hui Ju, focuses closely on preventing the bacteria’s movement, searching for Borrelia genes that can be mutated to produce the desired outcome; an exacting, tedious and long process with no particular timeline. He is proud of the many research papers his team has delivered to medical journals to advance knowledge on tick genetics.
“As a scientist, the potential for new discovery is motivational, and with so many steps in the search and elimination process, every day brings something different, producing new data,” Ju said. “Giving attention to one gene at a time, if you’re lucky you can knock out one gene in a year, but it can easily take two years.”
Theophilus prepares genes for mutation and proper identification, then transfers them into the normal Borrelia bacteria, hoping to mutate those.
“I was focused on studying borrelia genetics because they are very interesting and the research can produce big results,” she said. “It also contributes to the production of vaccines and molecules that can work against (Lyme disease).”
A tick must be attached and connected to a person’s blood stream for more than 20 hours for a sufficient number of the bacteria to become infiltrated into the body and adapt to the new environment, the scientists said. Theophilus offered some advice about watching out for the signs of the bite and infection, which are a bull’s-eye rash at the bite site, fever or flu-like symptoms.
“If you get to a doctor and treat Lyme disease quickly with antibiotics you don’t have to worry about it, but if you don’t it can become a chronic disease,” Theophilus said.