Researchers at UW-Madison are studying the reproductive cycle of a common parasite that poses a threat to fetuses, using new animal models to better understand the single-celled organism.
Toxoplasma gondii infects many different mammals, including humans, but can only reproduce inside the intestines of felines. Because of that, researchers have been somewhat limited in studying the parasite’s life cycle.
That’s according to Laura Knoll, the senior author of a new study and a professor of medical microbiology in the UW School of Medicine and Public Health. Her work was recently published in the journal Public Library of Science Biology.
Despite the parasite’s unique reproductive requirements, it’s extremely widespread, with nearly one-third of the human population chronically infected, UW-Madison says. But most people are unaware they’re infected, as the parasite seems to only pose a risk to fetuses whose mothers are infected.
“We’re a dead-end host,” Knoll said in a release. “It really isn’t a problem in people. I have it.”
People can get infections from handling cat litter, so pregnant women are generally warned against doing so. If the mother becomes infected, it can be transmitted to the fetus with “potentially fatal or serious developmental consequences,” the release shows.
Knoll and fellow researchers first attempted to grow the parasite using cat intestinal cells in culture but failed due to a missing ingredient: linoleic acid, a fatty acid that’s essential for human life.
Linoleic acid is broken down in the intestines of people and most animals with the help of an enzyme called delta-6-desaturase, or D6D. According to the release from UW-Madison, felines lack D6D activity in their intestines, meaning their intestines contain much more linoleic acid than those of other animals.
After the first unsuccessful attempt at growing Toxoplasma gondii, Knoll’s team used an inhibitor to suppress the D6D enzyme in mice and also added more linoleic acid to their diets, in order to get the parasite to reproduce in the smaller animal model.
Knoll says the approach her team is taking isn’t something most labs can do, as the inhibitor drug used to reduce the effect of the D6D enzyme can cost up to $300 per mouse. To overcome that obstacle, Knoll hopes to use gene-editing technology called CRISPR to create mice that don’t produce the D6D enzyme, so they can be readily used to study the parasite.
“We’ll basically be making a cat-mouse,” Knoll said. “It will help get around the issue of cost.”
