"The most exciting practical implication of this work is that it identifies a potential drug target that is quite different from anything that is targeted by existing antimalarial drugs," Blackman says. "This is very important, since it is widely agreed that the best way to prevent the appearance of drug resistance in any pathogen is to use combinations of drugs that target distinct biochemical pathways."
The most severe form of malaria, a disease that affects over 300 million people annually, is caused by the single-celled parasite Plasmodium falciparum, which was the focus of the study.
A number of different proteins on the surface of malaria parasites help the invaders bind to red blood cells. But once attached to host blood cells, the parasites need to shed the "sticky" surface proteins that would otherwise interfere with entrance into the cell.
"What we have discovered is the parasite enzyme -we refer to it as a 'sheddase'- which sheds the sticky proteins," says Michael Blackman, senior author of the study and parasitologist at London's National Institute for Medical Research. The enzyme, called PfSUB2, is required for the parasites to invade cells; without it, the parasites die.
The results also shed light on the fundamental mechanisms malaria parasites use to infect cells. "The malaria parasite is related to several other major pathogens, all of which invade cells in a similar manner, so work such as this can have wide-ranging implications," according to Blackman.
Blackman's team has worked on malarial surface proteins for over 15 years. "We predicted that this enzyme must have the capacity to 'move' across the surface of the parasite, since the proteins that are shed are themselves distributed all over the parasite surface," he says
Contact: Tim Sullivan
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