Discovery of malaria parasite escape technique leads to new drug target
13 December 2007
A breakthrough in understanding how the malaria parasite passes from cell to cell in the bloodstream has provided a new target for improved anti-malarial drug design.
Scientists led by Dr Mike Blackman of the Medical Research Council’s National Institute for Medical Research (NIMR) have identified an enzyme that if inhibited stops spread of the parasite. The results are published in Cell.
The team discovered that the enzyme, named PfSUB1, triggers release of the parasite from infected red blood cells thereby enabling it to invade new cells. Until now little has been known about how the parasite ruptures the old red blood cell to make its escape.
Further experiments found that a chemical compound that blocks the action of PfSUB1 prevents the parasite from bursting out of the cell and spreading.
‘‘Malaria threatens the lives of hundreds of millions of people and causes around 3 million deaths each year, mostly among young children in the developing world. The identification of this enzyme could lead to new treatments for what is one of the world’s most devastating infectious diseases,’’ said Dr Blackman of NIMR’s Division of Parasitology.
The Plasmodium falciparum parasite that causes malaria multiplies inside red blood cells until the daughter parasites, known as merozoites, are ready to infect other cells.
The team have discovered that merozoites contain a set of previously unrecognized cell subunits called exonemes that are packed full of the PfSUB1 enzyme. The enzyme is a protease, this means it has properties that enable it to destroy existing cell structures and in doing so allows the parasite to escape the red blood cell and go on to infect others.
Dr Blackman described how the team’s discoveries could be exploited in the fight against malaria:
“Malaria parasites are becoming increasingly resistant to conventional drug therapy, and there is an urgent need to develop new treatments based on an in-depth understanding of the biology of the parasite. Our work has shown that the enzyme PfSUB1 plays a critical role in regulating release of the merozoites that go on to invade other red blood cells. We also now know that PfSUB1 is a druggable parasite target so we hope to find drugs that will inactivate the enzyme and in doing so block the blood-stage life-cycle of the malarial parasite.”
The research involved close collaboration with the Drug Discovery Group of MRC Technology, the technology commercialisation arm of the MRC. Dr Blackman’s team hope that their discovery will set the scene for development of drugs that inhibit PfSUB1 to prevent and treat malaria.
Original research paper: Subcellular discharge of a serine protease mediates release of invasive malaria parasites from host erythrocytes is published online in Cell.
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