Toxoplasma Research Offers Potential for a Range of Benefits

For IU School of Medicine scientist William J. Sullivan, Jr., Ph.D., focusing his research on the parasite Toxoplasma gondii has turned out to be, in his words, “a complete win-win situation.”

It’s a win because his work is identifying potential routes to new, more effective treatments against the parasite and the damage it can do.

It’s a win because Toxoplasma is a model organism for the malaria parasite Plasmodium, meaning much of what is learned about Toxoplasma could lead to new treatments for a disease that struck 243 million people worldwide in 2008, and caused 863,000 deaths.

William J. Sullivan, Ph.D.

It’s also a win because on a basic science level, Toxoplasma has much to teach about cellular biology.

An estimated 60 million people in the United States are infected with the toxoplasmosis parasite, but in most cases the infection produces flu-like symptoms or no symptoms at all. However, for people with immune system problems – such as those undergoing chemotherapy or people with AIDS – the disease can cause serious effects including lung problems, blurred vision and seizures. Also, infants born to mothers who are infected for the first time during or shortly before pregnancy are at risk for severe complications, miscarriages or stillbirths.

One of the most common routes to human infection is via cats, in particular their feces or litter. Eating undercooked meat from infected livestock can also result in human infection.

Although there are anti-parasitic drugs available to treat acute episodes of toxoplasmosis, it’s currently impossible to completely eliminate the parasite because it can switch from an active to a latent cyst form in the body.  How Toxoplasma does that is key to the research in Sullivan’s lab.

Sullivan, associate professor of pharmacology and toxicology, and collaborator Ronald C. Wek, Ph.D., professor of biochemistry and molecular biology, have published several papers recently reporting discoveries about a molecular stress response pathway that Toxoplasma appears to use when it transforms to the cyst state – and to help it survive when it moves from one host cell to another. A collaboration with Victor Nussenzweig, M.D., Ph.D., of New York University produced a paper recently illuminating a similar role for the same pathway in Plasmodium, the malaria parasite.

Developing a small molecule drug that would disrupt that pathway is one route Sullivan and his colleagues are taking in hopes of developing treatments. A second approach is development of an animal vaccine to prevent transmission via meat products or cats.

Third, a preventative compound that kept the parasite bottled up in its cyst stage would be invaluable for people who have the parasite in cyst form then are hit by immune system problems, such as a round of chemotherapy.

The translational potential for new therapies is just one of the exciting challenges of working with Toxoplasma, said Sullivan.

“Toxoplasma is a very ancient eukaryote cell, so a lot of what we do teaches us about our own cells because it allows us to look at these molecular pathways in an organism that’s essentially a living fossil. We can see how these stress response pathways looked in a very early, primitive organism,” he said.

“We can satisfy our curiosity about cell physiology in general, and evolutionary biology, while at the same time the phenomena we’re studying could be used for very profound medical benefits.”