This was discovered by researchers from the University of California, Riverside Toxoplasma gondiia widespread parasite estimated to infect up to one-third of the world’s population is far more complex than scientists once believed. The study, published in The nature of communicationsheds new light on how the parasite causes disease and why it remains so difficult to eliminate with current treatments.
People most often become infected with toxoplasmosis by eating undercooked meat or by contact with contaminated soil or cat feces. Once inside the body, the parasite is known for its ability to evade detection by forming microscopic cysts, primarily in the brain and muscle tissue.
In most cases, infected individuals never experience noticeable symptoms. Even so, the parasite remains in the body for life, enclosed inside cysts that can contain hundreds of parasites. These dormant forms can later reactivate, especially in people with weakened immune systems, sometimes leading to serious complications affecting the brain or eyes. Infection during pregnancy poses additional risks because it can cause serious health problems in developing babies with immature immune systems.
Cysts are not as simple as once thought
For many years, scientists assumed that each cyst contained a single, uniform type of parasite that remained inactive until it reawakened. Using advanced single-cell analysis, the UC Riverside team found that assumption was incorrect. Their research shows that each cyst contains multiple parasite subtypes, each performing different biological functions.
“We found that the cyst is not just a silent shelter — it’s an active center with different types of parasites focused on survival, spread or reactivation,” said Emma Wilson, professor of biomedical sciences at the UCR School of Medicine and lead author of the study.
Inside the structure of toxoplasma cysts
Wilson explained that the cysts develop gradually as the immune system puts pressure on the parasite. Each cyst is surrounded by a protective wall and is filled with hundreds of slow-growing parasites known as bradyzoites. While the cysts are microscopic, they are relatively large compared to other intracellular pathogens, averaging up to 80 microns. Individual bradyzoites measure about five microns in length.
These cysts are most commonly found in neurons, but they also often appear in skeletal and cardiac muscle. This detail is particularly important because people are often infected by eating undercooked meat that contains these cysts.
Why cysts are important to disease and treatment
According to Wilson, cysts play a central role in both disease progression and transmission. Once formed, they resist all current therapies and persist in the body indefinitely. They also aid in the spread of the parasite between hosts.
When the cysts are reactivated, the bradyzoites transform into rapidly multiplying tachyzoites that move around the body. This process can lead to serious diseases such as toxoplasmic encephalitis (neurological damage) or retinal toxoplasmosis (loss of vision).
Rethinking the life cycle of Toxoplasma
“For decades, the life cycle of Toxoplasma was understood in overly simplistic terms, conceptualized as a linear transition between the tachyzoite and bradyzoite stages,” Wilson said. “Our research challenges this model. By applying single-cell RNA sequencing to parasites isolated directly from cysts in vivo, we found unexpected complexity within the cyst itself. Rather than a uniform population, cysts contain at least five different subtypes of bradyzoites. Although all are classified as bradyzoites, they are functionally distinct, with specific subsets primed for reactivation and disease.”
Overcoming long-standing research barriers
Studying cysts has historically been difficult. They develop slowly, are deeply embedded in tissues such as the brain, and are not produced efficiently in standard laboratory cultures. Because of these issues, most past research has focused on tachyzoites grown in vitro, leaving the biology of cyst-dwelling bradyzoites largely unexplored.
“Our work overcomes these limitations by using a mouse model that closely mirrors natural infection,” Wilson said. “Because mice are the natural intermediate host of Toxoplasma, their brains can contain thousands of cysts. By isolating these cysts, enzymatically digesting them, and analyzing individual parasites, we were able to gain insight into chronic infection as it occurs in living tissue.”
Implications for future treatment
Wilson noted that while current drugs can control the fast-growing form of the parasite responsible for acute illness, they cannot eliminate the cysts.
“By identifying the different subtypes of parasites inside the cysts, our study determines which ones are most likely to reactivate and cause damage,” she said. “This helps explain why past drug development efforts have struggled and suggests new, more precise targets for future therapies.”
Ongoing risks and shifting focus
Congenital toxoplasmosis remains a serious problem when the infection first occurs during pregnancy, as it can lead to serious fetal complications. Although prior immunity usually protects the fetus, routine screening is not available in some countries, highlighting the challenges of managing an infection that is widespread but often asymptomatic.
Despite how common toxoplasmosis is, it receives much less attention than many other infectious diseases. Wilson hopes the findings will help change that.
“Our work is changing the way we think about the Toxoplasma cyst,” she said. “It recasts the cyst as a central checkpoint in the parasite’s life cycle. It shows us where to target new treatments. If we really want to treat toxoplasmosis, the cyst is where we should be targeting.”
Study and funding details
Wilson conducted the study along with Arzu Ulu, Sandeep Srivastava, Nala Kachour, Brandon H. Le, and Michael W. White. Wilson and White are co-correspondents.
The research was funded by grants from the National Institute of Allergy and Infectious Diseases of the State Institute of Health. The article is titled “Bradyzoite Subtypes Rule the Crossroads of Toxoplasma Evolution.”
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