How to defeat a hijacking parasite

Researchers have discovered how Toxoplasma, a common parasite transmitted by cats, hijacks host cells and stockpiles food so it can lie dormant for decades — possibly changing its host’s behaviour in the process.

The two related research projects, published in the journals Cell Host & Microbe and eLife, were led by scientists from the Walter and Eliza Hall Institute (WEHI). The findings could lead to a vaccine to protect pregnant women from Toxoplasma infection, which carries a serious risk of miscarriage or birth defects, as well as drugs to clear chronic infections in people with compromised immune systems.

WEHI researcher Dr Chris Tonkin explained that Toxoplasma requires a human host cell — such as a brain cell (neuron) — to live in. The parasite hijacks this host cell to enable its own growth and survival, hibernating for decades by creating its own food reserve.

“Toxoplasma infection leads to massive changes in the host cell to prevent immune attack and enable it to acquire a steady nutrient supply,” Dr Tonkin said. “The parasite achieves this by sending proteins into the host cell that manipulate the host’s own cellular pathways, enabling it to grow and reproduce.”

Dr Justin Boddey added that some of these proteins might even influence the behaviour of the host, noting, “There is a fascinating association between Toxoplasma infection and psychiatric diseases, including schizophrenia and bipolar disorder. It is now possible to test whether proteins sent from the hibernating parasite into a host neuron disrupt normal brain function and contribute to development of these diseases.”

Once Toxoplasma parasites establish infection, they can lie dormant in our bodies for the rest of our lives. In people with suppressed immune systems, such as cancer patients, the parasite can reactivate and cause neurological damage and even death.

But Dr Tonkin said the teams’ discovery that the parasites stockpile large amounts of starch when they become dormant — similar to animals preparing for hibernation — could be used against them.

“By identifying and disabling the switch that drives starch storage, we found that we could kill the dormant parasites, preventing them from establishing a chronic infection,” he said, suggesting the finding could lead to a drug to clear chronic Toxoplasma infections or even a vaccine to prevent infection in at-risk people.

Dr Boddey added that the researchers have also discovered how the Toxoplasma parasite transported proteins into the host, explaining, “Our study showed that the parasite includes a signature on the exported proteins that ‘earmark’ them for transport into the host cell.

“Blocking transport makes the parasite much less dangerous in infection models, suggesting this may also be a new way of treating Toxoplasma infections.”

Image caption: Dr Chris Tonkin. Image credit: Walter and Eliza Hall Institute.

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