Blocking parasites in host cell may provide new way to fight malaria

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Washington, Apr 4 (ANI): Researchers at the University of Pennsylvania have discovered a new way to fight malaria - locking the disease-causing parasite inside the host cells.

Led by Dr. Doron Greenbaum, Assistant Professor of Pharmacology in the Penn School of Medicine, the researchers found that parasites hijack host-cell proteins to ensure their survival and proliferation.

They found that malarial parasites depend upon an enzyme stolen from the host cell for successful infection, and thus paved the way for developing a new route of attack.

"Researchers can now develop ways to kill parasites by placing roadblocks in the path they use to destroy their victims," said Greenbaum.

Starting with Plasmodium falciparum, which causes the most deadly form of human malaria, the researchers broadened their research to include Toxoplasma gondii, which causes a parasitic disease called toxoplasmosis.

Greenbaum said: "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's an ingenious system. Our findings open up whole new window for drug discovery."

As Plasmodium and Toxoplasma kill infected cells, they need to constantly hop from cell to cell to survive.

Scientists, however, still do not know what proteins the parasites use as tools to help them break through the walls of the cell.

To observe the behaviour of P. falciparum parasites, the research team infected human red blood cells, using pharmacological and biochemical evidence to discover that parasites activate the host protease calpain-1.

Blocking or removing calpain-1, a calcium-regulated protease, left parasites trapped inside the host cell. By adding calpain-1 back into the cell, parasites could once again blast free.

For knowing T. gondii's behaviour, the researchers infected mouse fibroblasts with T. gondii and used genetic techniques to remove, and restore, calpain activity.

It was found that in the absence of calpain, parasites could not escape the infected cell, just as they had observed for malaria parasites.

The researchers concluded that targeting host proteins instead of the parasite itself might give the parasite less scope to develop resistance, since the parasite doesn't have genetic control over host proteins.

Greenbaum is planning to continue exploring the viability of calpain as a drug target for antiparasitic drugs.

The study has been published in the online issue of the journal Science. (ANI)

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