Keeping Malaria Locked Up


Animal parasites such as malaria have complex life cycles and, so far, most attempts to control infection have centred on preventing the parasite from entering host cells. Writing in the journal Science, a team led by Dr Doron Greenbaum at the University of Pennsylvania has now focussed on an alternative treatment approach – locking the parasites inside the host cell. The team found that Plasmodium falciparum, prison barsthe species responsible for the majority of human infections, and also the one that causes the most virulent form of malaria, uses a host protease to escape from cells. The protozoa replicate within a vacuole in infected cells and must escape to begin a new lytic cycle. The team used a variety of techniques to show that P falciparum makes use of host cell calpain proteases to facilitate escape.

The team were also interested to find out whether the distantly related parasite, Toxoplasma gondii adopts a similar strategy. Disease caused by T gondii infection is usually mild and self-limiting, but can be fatal to the unborn child if contracted during pregnancy. They found that in the absence of calpain, the parasites could not escape the infected cell, just as they had observed for malaria parasites.

Greenbaum plans to continue to explore the practicality of calpain as a target for anti-parasitic drugs. P falciparum has become increasingly resistant to anti-malarial drugs and targeting a host protein may afford less scope for the development of resistance. Calpains are a family of calcium-dependent cysteine proteases whose physiological roles are poorly understood.

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