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Stress helps homeless parasite survive

INDIANA U. (US)— The parasite responsible for toxoplasmosis requires a stress response system that helps it survive the move to infect new cells.

The discovery could lead to new treatments to control the disease, researchers say.

Parasites such as Toxoplasma gondii invade host cells, replicate, and then must exit to find new host cells to invade.

Traveling outside their host cell exposes the parasites to environmental stresses that limit how long they can remain viable

“Toxoplasma does not like to be homeless,” says William Sullivan Jr., associate professor of pharmacology and toxicology at Indiana University.

“Being deprived of the nutrients and shelter provided by the host cell is a serious stress on the parasite. Our research uncovered a critical pathway the parasite uses to survive the journey from one host cell to another.”

The parasite triggers a stress response mechanism that alters protein production through phosphorylation of a factor called eIF2, which the Toxoplasma parasite uses to survive periods when it finds itself without a host cell.

Phosphorylation is a cellular process in which a phosphate compound is added to a protein to alter its activity.

The study appears in the online early edition of Proceedings of the National Academy of Sciences.

Based on earlier research, the group previously reported that the same response system is employed by the parasite when its host cell is stressed, which enables Toxoplasma to transform into a cyst surrounded by a protective barrier that can resist drugs and the body’s immune system.

Later, however, the parasite is able to emerge from its dormant state to strike when a patient’s immune system is weakened.

“Our latest findings indicate that if we design new drugs that target this stress response pathway, these drugs may be effective against both acute and chronic Toxoplasma infection,” says Sullivan.

An estimated 60 million people in the United States are infected with the toxoplasmosis parasite. For most, the infection produces flu-like symptoms or no symptoms at all.

However, for people with an impaired immune system—such as those undergoing chemotherapy, heart transplants, or people with AIDS—the disease can cause life-threatening complications including cardiopulmonary problems, blurred vision, and seizures.

Also, if a woman becomes infected for the first time shortly before or during pregnancy, there is risk of miscarriage or congenital birth defects.

Support for this research was provided through grants from the American Heart Association and the National Institutes of Health.

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