WHEI researchers have discovered how a common parasite hijacks host cells and stockpiles food so it can lie dormant for decades, possibly changing its host’s behavior or personality in the process.

 


Picture a tiny, single-celled organism that resides undetected within its host for decades. Suddenly, the host falls ill, and the parasite seizes its chance to burst onto the scene and replicate itself en masse, pushing the host to the brink of death and sometimes beyond. Sounds like the synopsis of a new Ridley Scott film? Unfortunately, it is an all too real scenario for those infected with the parasite Toxoplasma gondii.

However now, researchers from the Walter and Eliza Hall Institute of Medical Research (WEHI) have uncovered how this devious little parasite hijacks host cells and stockpiles food so it can lie dormant for decades, possibly even changing its host's behavior or personality in the process.

The investigators are hopeful that the results from their study will lead to a vaccine to protect pregnant women from Toxoplasma infection—which carries a serious risk of miscarriage or birth defects— as well as new therapeutics to clear chronic infections in people with compromised immune systems, such as cancer and HIV patients.       

Once inside a mammalian host the parasite often resides and hibernates within neurons of the brain. The WEHI team discovered how the parasite hijacks the host cell to enable its growth and survival, hibernating for decades by creating its own food reserve.

Toxoplasma infection leads to massive changes in the host cell to prevent an immune attack and enable it to acquire a steady nutrient supply,” explained senior author Chris Tonkin, Ph.D., laboratory head in the division of infection and immunity at WEHI. “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.”

Many researchers feel that these proteins may even influence the behaviors of the host, and there has been previous work to study how Toxoplasma-infected mice act in comparison to their uninfected littermates. 

“There is a fascinating association between Toxoplasma infection and psychiatric diseases including schizophrenia and bipolar disorder,” remarked Justin Boddey, Ph.D., laboratory head in the division of infection and immunity at WEHI. “It is now possible to test whether proteins sent from the hibernating parasite into a host neuron disrupt normal brain function and contribute to the development of these diseases.”

The findings from this study were published recently in Cell Host & Microbe through an article entitled “Regulation of Starch Stores by a Ca2+-Dependent Protein Kinase Is Essential for Viable Cyst Development in Toxoplasma gondii.”

T. gondii is a common parasitic infection that is transmitted by cats and often found in raw meat. The global burden of Toxoplasma infections is significant with an infection rate close to 30%. Like many parasites in the phylum Apicomplexa—which is composed of a vast array of medically important organisms such as the malaria parasite Plasmodium and Cryptosporidium, a parasite of the mammalian intestinal tract—T. gondii undergoes a two-stage lifecycle. The sexual stage takes place within feline species and the asexual stage that is completed in a mammalian host.

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. Dr. Tonkin said the team identified pathways that allow the parasite to establish chronic infections. 

“We discovered that, similar to animals preparing for hibernation, Toxoplasma parasites stockpile large amounts of starch when they become dormant,” noted Dr. Tonkin. “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.”

The WEHI team is hopeful that their discovery will eventually open the door to a Toxoplasma vaccine, preventing infection n at-risk people, such as pregnant women.

“Cats are one of the primary transmitters of Toxoplasma parasites,” Dr. Tonkin said. “If the parasites are transmitted to pregnant women, for example through contact with kitty litter, there is a substantial risk of miscarriage or birth defects. We hope to use our discoveries to develop a vaccine that stops cats transmitting the parasite, to prevent these potentially catastrophic consequences.”

The investigators were also excited to unravel a long-standing mystery about how T. gondii parasites transported proteins into the host.

“Our study showed that the parasite includes a signature on the exported proteins that 'earmark' them for transport into the host cell,” Dr. Boddey stated. “Blocking transport makes the parasite much less dangerous in infection models, suggesting this may also be a new way of treating Toxoplasma infections.”







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