A study in Nature Communications reveals that Toxoplasma gondii cysts are not a dormant reservoir but a diverse system of subtypes, which may explain why there is currently no treatment that eradicates the cysts.
A common parasite hiding in the brain turns out to be much more active, organized, and diverse than we previously thought.
A team of researchers from the University of California – Riverside reports that Toxoplasma gondii (Toxoplasma gondii), a parasite estimated to infect up to a third of the world's population, exhibits much greater biological complexity than previously understood. The findings, published in the journal Nature Communications, provide new insights into how the parasite causes disease, and why it has been so difficult to eradicate with existing treatments.
How toxoplasmosis spreads in humans
Humans are most often infected with toxoplasmosis by eating undercooked meat, or by coming into contact with contaminated soil or cat feces. Once the parasite enters the body, one of its key features is its ability to evade the immune system by forming tiny cysts, most often in the brain and muscle tissue.
In most people infected, the infection does not cause noticeable symptoms. However, the parasite remains in the body for life within those cysts, each of which can contain hundreds of parasites. Under certain conditions – and especially when the immune system is weakened – the parasites may “reawaken” and cause serious damage to the brain or eyes. Infection during pregnancy is particularly dangerous, because it can lead to serious complications in the fetus and newborns whose immune systems are not yet mature.
Inside the cysts: not a “dormant state,” but a diverse system
For years, the common assumption was that each cyst contained a single, uniform type of parasite that remained dormant until reactivated. However, using advanced single-cell analysis techniques, researchers at the University of California, Riverside have found that this assumption is incorrect. The findings suggest that each cyst contains several different subtypes of parasites, each with a different biological function.
“We discovered that the cyst is not just a quiet hiding place – it is an active hub that houses different types of parasites, geared towards survival, proliferation or reactivation,” said Emma Wilson, professor of biomedical sciences at the university’s School of Medicine and lead author of the study.
Wilson explains that the cysts form gradually as the parasite responds to stress from the immune system. Each cyst is enveloped in a protective shell and contains hundreds of slowly growing parasites, called bradyzoites. Although the cysts are microscopic, they are large relative to other intracellular pathogens: a cyst can be up to 80 micrometers in diameter, and a single bradyzoite is about five micrometers long.
The cysts are most often found within neurons, but also appear in skeletal and cardiac muscle. This is important because one of the common routes of infection in humans is through eating undercooked meat containing cysts.
Why cysts “last” and what it means for treatments
According to Wilson, cysts play a central role in both causing the disease and transmitting the parasite between hosts. Once established, they are resistant to all currently available treatments and can remain in the body indefinitely.
When cysts are reactivated, the bardyzoites transform into tachyzoites, a form that multiplies rapidly and spreads throughout the body. This process can cause serious diseases, such as toxoplasmosis encephalitis (neurological damage) or retinal toxoplasmosis (up to vision loss).
“For decades, the Toxoplasma life cycle has been overly simplistically understood as a linear transition between tachyzoite and bardizoite stages,” said Wilson. “Our study challenges this model. By sequencing single-cell RNA from parasites isolated directly from cysts in vivo, we found unexpected complexity within the cyst itself. Rather than a uniform population, the cysts contain at least five distinct subtypes of bardizoites. Although all are classified as bardizoites, they are functionally distinct, and some subsets are particularly ‘primed’ for reactivation and disease.”
Wilson notes that cysts have been difficult to study for years: they grow slowly, are buried deep within tissues such as the brain, and are not efficiently formed in standard laboratory cultures. As a result, much of the genetic and molecular research in the field has focused on tachyzoites grown in vitro—while the bardyzoites that reside within cysts have remained less well understood.
“Our work overcomes these limitations by using a mouse model that closely mirrors natural infection,” she said. “Mice are natural intermediate hosts for Toxoplasma, and their brains can contain thousands of cysts. By isolating the cysts, enzymatic digestion, and analyzing individual parasites, we were able to obtain a picture of chronic infection as it occurs in living tissue.”
As for future treatments, Wilson explains that current drugs can control the rapidly multiplying form of the parasite that causes acute disease—but there is no drug that can eliminate cysts. “Identifying different subtypes within the cysts allows us to understand precisely which ones are more likely to reproduce and cause damage,” she says. “This helps explain why past drug development attempts have failed, and offers new, more precise targets for future treatments.”
Congenital toxoplasmosis remains a significant concern when the first infection occurs during pregnancy, as it can lead to serious consequences for the fetus. Although early immunity usually protects the fetus, routine testing is not available in all countries – a fact that highlights the challenge of managing a common infection, which often does not cause symptoms.
Despite its prevalence, toxoplasmosis has received less attention than many other infectious diseases. Wilson hopes the new findings will change that: “Our work changes the way we think about the Toxoplasma cyst. It repositions the cyst as the central control point in the parasite’s life cycle, and shows where new treatments should be aimed. If we really want to treat toxoplasmosis, the cyst is where we need to focus.”
Research source: "“Bardisozoite subtypes dominate a crossroads of toxoplasmosis evolution” By Erzu Ulu, Sandeep Srivastava, Nella Kachur, Brandon H. Le, Michael W. White and Emma H. Wilson, 2026-01-24, Nature Communications.
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