Indiana U scientists uncover potential key to better drugs to fight toxoplasmosi...( INDIANAPOLIS Discoveries by Indiana...)

INDIANAPOLIS Discoveries by Indiana University School of Medicine scientists have opened a promising door to new drugs for toxoplasmosis and other parasites that now can evade treatments by turning dormant in the body.

Their findings help explain how the parasite that causes toxoplasmosis transforms into a cyst form that resists drugs and the body's immune system, yet can emerge from its dormant state to strike when a patient's immune system is weakened.

Led by William J. Sullivan Jr., Ph.D., assistant professor of pharmacology and toxicology, and Ronald C. Wek, Ph.D., professor of biochemistry and molecular biology, the research team found a cellular signaling system that takes hold when the parasite is stressed, enabling it to transform into the cyst surrounded by a protective barrier.

The signaling system identified by the IU team could serve as a target to block the transformation into the cyst form or to attack the parasite while in the cyst form. Their report was published in the June 13 issue of the Journal of Biological Chemistry.

The Toxoplasma gondii parasite converts from an active state to the inactive cyst state when it is stressed, for example, by heat from fever. Stress response mechanisms have been well studied in yeast and other organisms, but the pathways used by the toxoplasmosis parasite had not been determined.

"We found a cellular signal that appears to put the parasite to sleep, which in turn tells us something new about how opportunistic pathogens such as Toxoplasma awaken to cause disease during immunosuppression," said Dr. Sullivan.

An estimated 60 million people in the United States are infected with the toxoplasmosis parasite, but for most infection produces flu-like symptoms or no symptoms at all. However, for people with immune system problems such as those undergoing chemotherapy or people with AIDS the disease can cause serious effects including lung problems, blurr
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