Scientists have developed a new fluorescent imaging method to track the growth of Toxoplasma gondii in real time, revealing its unusual cell cycle, which could help to develop new effective treatments.
A common parasite that infects nearly one-third of the world’s population has avoided in-depth study due to its microscopic size. Now, researchers have developed a new imaging approach that allows scientists to observe its growth in real time, which could lead to improved treatments.
The parasite, Toxoplasma gondii, causes toxoplasmosis, an infection that is usually mild but can pose serious risks to pregnant women and people with weakened immune systems. The new study, led by the University of South Florida, adapts fluorescent imaging techniques typically used in human cell research to track the parasite’s development.
A hidden threat with limited treatment options
Toxoplasma is commonly spread through undercooked meat or contaminated produce. While early-stage infections can be treated, options are limited once the parasite becomes chronic.
Toxoplasma is commonly spread through undercooked meat or contaminated produce.
“Though the parasite can be repressed in the acute stage, it requires drugs that can be toxic if taken long term,” said Elena Suvorova, an associate professor at the USF Health Morsani College of Medicine. “If you can’t catch toxoplasmosis during this time, the parasite turns chronic. In this stage, it hides from the immune system and forms cysts in the brain, for which there are currently no cures.”
The lack of effective long-term treatments has driven efforts to better understand how the parasite grows and spreads within the body.
An unusual and poorly understood cell cycle
One of the biggest challenges facing researchers has been Toxoplasma’s unconventional cell cycle. In most organisms, cells grow, duplicate their DNA and then divide into two identical cells in a predictable sequence.
“Toxoplasma doesn’t follow this standard pattern,” said co-author Mrinalini Batra, a research scientist involved in the study. “Scientists knew it had to go through similar stages because it reproduces but they didn’t know how those stages were arranged or whether they even existed in the same way as they do in human cells. That made it hard to understand how this parasite grows and spreads.”
Without a clear picture of this process, identifying ways to stop the parasite from multiplying has proved difficult.
Fluorescent breakthrough reveals growth stages
To overcome this, the research team adapted a fluorescent imaging system to track proteins linked to specific stages of the parasite’s growth. After extensive testing, they identified a protein known as PCNA1, located in the parasite’s nucleus, which changes behaviour as the organism progresses through its cycle.
After extensive testing, they identified a protein known as PCNA1, located in the parasite’s nucleus, which changes behaviour as the organism progresses through its cycle.
“When we attached two copies of a bright neon green tag to this protein, the signal became strong and clear,” Batra said. “This allowed us to determine the parasite’s stage simply by watching how the glowing protein behaved in the cell cycle. For the first time, researchers were able to clearly map Toxoplasma’s cell cycle.”
The findings demonstrated that while the early stages of growth follow a more conventional pattern, later stages overlap rather than occurring one after another.
“These latter stages are similar to a fork’s structure,” Suvorova said. “Toxoplasma’s cell cycle begins with one straight handle and then several prongs that branch off, allowing as many as three cell cycle phases to occur simultaneously. This unusual pattern helps the parasite multiply rapidly and evade the host’s immune system before forming cysts in the brain.”
Pathway to new treatments
By mapping the parasite’s life cycle in detail, researchers now hope to identify vulnerabilities that could be targeted by new therapies. The team is already investigating how different drugs affect specific stages of the cycle, with the aim of developing safer and more effective treatments.
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