Intracellular Parasites Require the Lytic Activity of Host-Cell Calpains

The parasites required the activity of host-produced calpain-1 in order to destroy the host cell. Calpains, which are a family of calcium-dependent, non-lysosomal cysteine proteases, are active participants in processes such as cell mobility and cell cycle progression, as well as cell-type specific functions such as long-term potentiation in neurons and cell fusion in myoblasts. Other reported roles of calpains are in cell function, helping to regulate clotting and the diameter of blood vessels, and playing a role in memory. Calpains have been implicated in apoptotic cell death, and appear to be an essential component of necrosis.

The investigators used biochemical techniques to demonstrate that destruction of erythrocytes by Plasmodium and genetic techniques to show that escape of Toxoplasma from fibroblasts were both dependent on calpain-1 activity.

"We always suspected that enzymes called proteases might be required to help parasites escape from the infected cell, but had assumed that these enzymes were produced by the parasites themselves. We had never considered that parasites might instead hijack host cell proteases. It is an ingenious system," said senior author Dr. Doron Greenbaum, assistant professor of pharmacology at the University of Pennsylvania. "Our findings open up whole new window for drug discovery."

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