A research team from the University of California, Riverside has found that Toxoplasma gondii, a parasite affecting up to one-third of people worldwide, is more complex than previously thought. The study, published in Nature Communications, offers new understanding of how the parasite causes disease and why it remains difficult to treat.
Toxoplasmosis, the disease caused by T. gondii, is often contracted through undercooked meat or exposure to contaminated soil or cat feces. While most infected individuals do not experience symptoms, the parasite can remain in the body for life as cysts in the brain and muscles. These cysts can become active again later on, especially in those with weakened immune systems or during pregnancy, sometimes leading to severe complications.
Until this study, scientists believed that each cyst contained only one type of dormant parasite. Using advanced single-cell analysis methods, the UC Riverside researchers discovered that each cyst actually holds several distinct subtypes of parasites with different biological functions.
"We found the cyst is not just a quiet hiding place - it's an active hub with different parasite types geared toward survival, spread, or reactivation," said Emma Wilson, professor of biomedical sciences at UCR School of Medicine and lead author of the study.
Wilson explained that these cysts form slowly under pressure from the immune system and are surrounded by a protective wall. Each cyst contains hundreds of bradyzoites—slow-replicating forms of the parasite—which primarily reside within neurons but are also found in skeletal and cardiac muscle tissue. This is significant because humans can become infected by eating undercooked meat containing such cysts.
The presence of these cysts is clinically important for several reasons: they are resistant to all current treatments and persist once established; they enable transmission between hosts; and when reactivated, they transform into fast-replicating tachyzoites that spread throughout tissues and can cause serious diseases like toxoplasmic encephalitis or retinal toxoplasmosis.
Studying these cysts has been challenging due to their slow growth and deep location within tissues such as the brain. Most previous studies have focused on tachyzoites grown outside living organisms rather than on bradyzoites inside actual tissue.
"Our work overcomes those limitations by using a mouse model that closely mirrors natural infection," Wilson said. "Because mice are a natural intermediate host for Toxoplasma, their brains can harbor thousands of cysts. By isolating these cysts, digesting them enzymatically, and analyzing individual parasites, we were able to gain a view of chronic infection as it occurs in living tissue."
Currently available treatments can control only the fast-growing form responsible for acute illness; no existing drugs eliminate persistent cysts.
"By identifying different parasite subtypes inside cysts, our study pinpoints which ones are most likely to reactivate and cause damage," Wilson said. "This helps explain why past drug development efforts have struggled and suggests new, more precise targets for future therapies."
Congenital toxoplasmosis continues to be a concern if infection occurs during pregnancy since it may result in serious fetal health problems. Routine screening varies across countries despite prior immunity typically offering protection for fetuses.
Despite its high prevalence globally—affecting up to one-third of people—toxoplasmosis receives less attention compared to other infectious diseases.
"Our work changes how we think about the Toxoplasma cyst," Wilson said. "It reframes the cyst as the central control point of the parasite's life cycle. It shows us where to aim new treatments. If we want to really treat toxoplasmosis, the cyst is the place to focus."
Other contributors include Arzu Ulu, Sandeep Srivastava, Nala Kachour, Brandon H. Le, and Michael W. White; both Wilson and White served as co-corresponding authors on this paper. The research was funded by grants from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.
