Malarial Achilles Heel

17 June 2009
Posted by Chris Smith.

Researchers in Australia have uncovered a cellular linchpin that malaria uses to hijack its hosts. Writing in Nature, Melbourne-based Walter and Eliza Hall Institute researcher Tania de Koning-Ward and her colleagues explain how they have identified a specialised pore that is used by malaria to manipulate the blood cells in which it grows, clearing up a long-standing mystery. A mosquito biting a fingerThe mosquito-spread parasite, which causes over 200 million infections and 2 million deaths annually, grows inside a bubble-like structure called a vacuole within red blood cells. This enables the parasite to control its own environment very closely but the question has always been how do materials and proteins made by the parasite get through the vacuole membrane to alter the behaviour of the infected blood cell? This is important because one of the strategies adopted by malaria is to add the molecular equivalent of Velcro to the surfaces of infected cells so that they jam in small capillaries including those in the brain and kidney. This helps to keep the parasite out of the clutches of the immune system, but it can also be lethal for the affected individual in whom it can trigger strokes and kidney failure. But now the Australian team have discovered how it's done. They've found that the parasite makes a cluster of proteins that assemble themselves into a pore-like structure known as a translocon, which sits astride the membrane surrounding the parasite. This translocon, dubbed PTEX, can recognise a characteristic "label" which is carried by all of the malarial proteins that need to be exported into the hijacked cell. Using this label, the pore selectively picks up the appropriate proteins and threads them through itself. Critically, the structure of PTEX appears to be unique to malaria, suggesting that it should be possible to find drugs that can selectively block it. In this respect it might hold the key to a host of new anti-malarial agents, and right on cue too, since, owing to rising resistance, the anti-malarial medicine chest is currently very bare.

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