University of Rhode Island entomologist Jannelle Couret is tipping the way we understand the bacteria that causes Lyme disease. Instead of looking at it from the human perspective, she and an interdisciplinary team of researchers are taking the view of the tick.
While the bacteria – Borrelia burgdorferi – is the pathogen that causes Lyme disease in humans, its presence is quite different in blacklegged ticks that pick up the bacteria from feeding on white-footed mice. For the ticks, the bacteria doesn't cause disease. It might even be beneficial.
For the next four years, Couret's team will research the ecological factors driving the evolution of Borrelia burgdorferi in blacklegged ticks thanks to a $2.6 million grant from the National Institutes of Health. The grant is part of the prestigious Ecology and Evolution of Infectious Disease (EEID) program, run by the NIH, National Science Foundation, and U.S. Department of Agriculture.
I am really interested in the factors that are driving the tick populations. Their populations vary year to year. Our preliminary data suggests that the survival of the ticks during some of their early life stages is improved based on whether they host these bacteria."
Jannelle Couret, assistant professor of biological studies and principal investigator on the grant
For the four-year study, Couret is collaborating with Associate Professor Sukanya Narasimhan of Yale Medical School, Associate Professor Jean Tsao of Michigan State University, and Associate Professor Cynthia Lord of the University of Florida – along with postdoctoral, graduate and undergraduate trainees at each institution.
"One of my favorite aspects of this work is the research team. We are all women and three of us are women of color," said Couret, who is part Indigenous, Afro-Cuban, and American. "I think that is – unfortunately – somewhat rare in science."
Blacklegged ticks, also called deer ticks, carry seven known pathogens and are responsible for about 95% of the tick-borne diseases in the U.S., including about 30,000 cases of Lyme disease reported each year. Deer ticks can acquire the bacteria that causes Lyme disease during any of its life stages – larvae, nymph or adult – during a blood meal from white-footed mice, the primary carriers of the Lyme disease bacterium. (While the abundance of deer ticks is casually associated with deer, these hosts do not transmit Borrelia burgdorferi to ticks, and deer are not considered an important host for the maintenance of the bacteria in wildlife populations.)
But the bacteria doesn't lead to Lyme disease in either the mice or the ticks. In pilot studies, Couret has seen changes in the ticks that acquire the bacteria – including behavior, metabolism, respiration, and survival. So there appears to be an advantage for those ticks, she said.
"That's a shift in mindset," said Couret, who joined URI in 2015 after earning her Ph.D. in the ecology of infectious diseases at Emory University. "We mainly think of Borrelia burgdorferi as a pathogen because it causes Lyme disease in humans. We are studying the transmission cycle of the bacteria in nature between ticks and white-footed mice. It's possible that it's not acting as a pathogen, but rather as a beneficial symbiont of the tick, a partner. The bigger picture question is, if we view Borrelia burgdorferi with this lens, can we better understand its transmission dynamics?"
In understanding the transmission cycle of Lyme disease, the researchers will explore the relationships of many influences on the bacteria in the tick, including environmental factors, such as temperature and humidity; ecological facets, such as the tick's microbiome; and the bacteria's interactions with other organisms in the tick.
"We're studying the effects of the bacteria on ticks at different levels, from gene expression to behavior,'' she said. "We'll combine that information to look at the evolutionary fitness of ticks, and model the impacts of bacteria on annual tick populations. We also are considering the microbiome. We want a really comprehensive view of the ensemble of ecological interactions that influence ticks, Borrelia burgdorferi, and their partnership."
For the study, Narasimhan, a molecular biologist, will look at gene expression to learn what is changing in the ticks that acquire the bacteria, along with what is changing in the bacteria. Lord, a vector-borne disease modeler, will incorporate the experiment results in a model that can predict tick populations and rates of transmission of Borrelia burgdorferi.
Tsao, a tick ecologist, will study deer ticks in the Midwest, another hot spot of Lyme disease. Paralleling Couret's work in Rhode Island, Tsao will study tick behavior and development in a semi-natural environment. Tsao and Couret will also look at traits that may be affected by the presence of Borrelia burgdorferi, effects of environmental conditions, survival rates, and gene expression.
When it's completed, the study will greatly expand our understanding of the factors driving the maintenance of Lyme disease in wildlife. Findings could eventually lead to ways to control the deer tick population or inform disease prevention measures, Couret said.
Also, by characterizing the role of the microbiome as it relates to tick-Borrelia interactions, the research could lead to novel methods of biological controls, such as finding competing bacteria within the tick that, when present, negatively impact Borrelia burgdorferi transmission.
A unique aspect of the grant is the heavy focus on providing comprehensive mentorship for trainees, centering the experiences of those who have been marginalized in science and supporting the team through professional development across all four institutions involved. Called the Microbiome Integrated Tick Ecology Network – or MITEY Network, as in mites – the mentoring will send trainees to each partner University to sharpen science skills, promote sustainable and productive writing practices and science communication, support a growth mindset, and reduce imposter syndrome.
"We want to make sure it's an inclusive research culture and environment for our trainees," Couret said.
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