Metabolic Changes Protect Parasite from Extracellular Stress

By experimentally mimicking the conditions experienced by the parasite Trypanosoma brucei, researchers have learned that cleavage of free glycosylphosphatidylinositol (GPI) is a critical first step that promotes the ability of the parasite to survive in the gut of the tsetse fly.

Cell exposure to hypo-osmolarity and alkalinity triggers a spectrum of responses, including activation of phospholipases. Of particular interest in the current study was the activation of glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC), which is expressed in T brucei, the protozoan parasite that causes human African trypanosomiasis. Conditions of hypo-osmolarity and alkalinity are found in the gut of the tsetse fly, which is the vector of the disease.

"We found that putting these cells under stress similar to that initially encountered by the trypanosome inside the fly caused the parasites to cleave free GPIs,” said Dr. Kojo Mensa-Wilmot, professor of cellular and molecular biology at the University of Georgia (Atlanta, USA), "and that gives us important information about how the trypanosome cell functions.”

Further observations published in the May 9, 2006, issue of the FEBS (Federation of European Biochemical Societies) Journal revealed that under these conditions there existed a novel mechanism for protein transport from glycosomes to the endoplasmic reticulum. "Before this work in trypanosomes, there was no evidence that we could ‘catch' peroxisome proteins moving to the endoplasmic reticulum, said Dr. Mensa-Wilmot. "With better understanding of the process, we could begin looking for compounds that may act as drugs by blocking the parasite's ability to respond to extracellular stress.”



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