Phosphorylation is the Key to Cyst Formation in Toxoplasma

Molecular parasitologists have identified the mechanism used by the protozoan parasite Toxoplasma gondii to transform into protective cysts that resist destruction by the immune system.

A key problem in the treatment of numerous pathogenic eukaryotes centers on their development into latent forms during stress. In a study published in the June 13, 2008, issue of the Journal of Biological Chemistry, investigators at the Indiana University School of Medicine (Indianapolis, USA) traced the mechanism used by the parasite T. gondii to transform into cysts and remain in this state.

They found that the Toxoplasma eukaryotic initiation factor-2-alpha (TgIF2-alpha) was phosphorylated during stress, which induced the parasite to transform into cysts. In addition, they characterized novel eIF2 kinases, one in the endoplasmic reticulum and a likely regulator of the unfolded protein response (TgIF2K-A) and another that is a probable responder to cytoplasmic stresses (TgIF2K-B). These findings suggest that eIF2-alpha phosphorylation is employed by cells to maintain a latent state.

"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 senior author Dr. William J. Sullivan, assistant professor of pharmacology and toxicology at the Indiana University School of Medicine. "A healthy immune system can keep this parasite in the cyst state. Without a healthy immune system, this organism can run rampant. This can be a very serious problem for people with AIDS.”


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