Toxoplasmosis, an infection that can cause miscarriages and birth defects and be deadly in people with weak immune systems, is hard to study because the parasite reproduces only in cats, which most labs avoid experimenting on for ethical reasons.
Now UW- Madison scientists have discovered why the parasite replicates sexually only in cat intestines. Using the new knowledge, they created cat-like lab mice to enable more research on the disease, a risk especially for pregnant women and people who eat undercooked meat.
The developments could help efforts to create a vaccine for cats. The work is timely because in April the U.S. Department of Agriculture shut down the main lab that was infecting cats with toxoplasmosis, following pressure from animal-testing critics.
The new mouse model “is not perfect; it’s not the cat yet, but it’s working really quite well,” said Laura Knoll, a UW-Madison professor of medical microbiology and senior author of the study, published online this month in the journal Public Library of Science Biology.
About 40 million Americans are thought to be infected with Toxoplasma gondii, or Toxo, the parasite that causes toxoplasmosis, according to the Centers for Disease Control and Prevention.
The vast majority of people are infected by eating undercooked meat — especially pork, lamb or venison — or shellfish.
Most people have no symptoms — such as swollen lymph nodes, muscle aches and vision problems — because their immune systems protect them. However, some studies suggest the infection, which resides in the brain, could contribute to schizophrenia, Knoll said.
People with compromised immune systems — including those on chemotherapy, with AIDS or who have received organ transplants — are particularly at risk.
Pregnant women, especially those who previously haven’t been infected with toxoplasmosis, are advised to avoid cat litter and stray cats. Women infected shortly before or during pregnancy can pass the infection to their fetuses, possibly leading to miscarriages or stillbirths, or babies with blindness or mental disabilities.
Hmong people are much more likely than whites to have two identical copies of genes that control certain immune response factors, greatly reducing their protection against the fungus that causes blastomycosis.
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Knoll and her colleagues tried unsuccessfully for years to get Toxo to reproduce in cat gut tissue in the lab. Suspecting a missing ingredient, they added linoleic acid — a fatty acid, or lipid, that had been removed from the cells to make the cells easier to study — and the parasites had sex.
Unlike the intestines of humans, mice and other mammals, cat guts lack an enzyme that processes linoleic acid, allowing the acid to build up and create a Toxo brothel of sorts.
“What we think is that because cats evolved in the desert, they wanted to conserve all their calories, and so they don’t make lipid mediators,” Knoll said.
Her research team, including post-doctoral fellow Bruno Martorelli Di Genova and graduate student Sarah Wilson from UW-Madison and J.P. Dubey, a researcher at the USDA lab in Maryland that closed in April, used an inhibitor to suppress the enzyme in mice and supplemented the mouse diet with linoleic acid.
In such mice, Toxo reproduced. The mouse feces contained a stage of the parasite called oocysts, though not as many as from cats.
Two compounds from a bacterium found on worms prevented mosquitoes from feeding in a campus lab experiment.
Knoll and her colleagues now hope to use the gene-editing technology CRISPR to make mice that don’t have any of the enzyme that processes linoleic acid in their guts.
The goal is to help scientists better study the life cycle of Toxo and develop a vaccine for cats, which could help people, too.
Knoll, who has two children ages 14 and 17, was tested for toxoplasmosis before she got pregnant because she worked in a lab handling the parasite. She was positive, meaning her immune system likely would have kept any new exposure from harming her children.
But most women aren’t tested before pregnancy, so they are told to be cautious around cats.
“It would be nice for women to be able to get their cats vaccinated before they wanted to start trying to get pregnant,” Knoll said.