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July 16, 2014

Study: Malaria Parasite Has Achilles Heel

by Joe DeCapua

Researchers say they have found a weakness in the malaria parasite that could lead to new drugs to block infection. The mosquito-borne disease kills more than 600,000 people every year, most of them in sub-Saharan Africa – and many of them children.

Listen to De Capua report on malaria parasite

“When the parasite infects a human it lives not just in your body, but actually inside of red blood cells," said Josh Beck, the first author of the study that appears in the July 16 edition of the journal Nature. "And within the red blood cells it will grow and all the problems that you get when you have malaria are a result of that growth in the red blood cell.”

The World Health Organization says there are five parasite species that cause malaria in humans. Plasmodium Falciparum is the most deadly.

Beck said it does not just invade the cell. It makes major renovations to its new home.

“Within the red blood cell the parasite lives inside of a little membrane compartment that’s like a little home for it. And to turn the red blood cell into a proper home for itself it makes all these different proteins that it sends out into the red blood cell that cause it to be modified in a variety of ways – structurally, metabolically," he said. "And these cause some of the disease symptoms that are associated with malaria.”

Beck, a postdoctoral research scholar at the Washington University School of Medicine in St. Louis, said researchers have known about the parasite proteins for some time. But they were not sure how the hundreds of different proteins actually left the parasite and entered the red blood cell. So they focused on a protein called HSP101 and found some answers. The proteins pass through a single pore in the parasite’s compartment.

“What we found,” said Beck, “is that it looks like it’s a bottleneck right there. Everything from all these diverse pathways funnels into this one specific pore.”

A potential roadblock, if you will.

“It is exciting because it suggests that this process could be broadly inhibited by targeting this one specific piece of parasite machinery,” he said. 

In lab experiments, when researchers blocked that pore the parasite stopped growing and eventually died. They describe it as “entombing the parasite.” To make that happen in infected people, however, will take a lot more work.

Beck said, “The way that it will be approached broadly in the field is by screening different small molecule compounds that could potentially be developed into drugs that would interfere with the action. There are a number of different aspects of this pore complex that could potentially be targeted. And so, there’s a lot of different ways to think about designing drugs.”

New malaria drugs will be needed. The World Health Organization warns the parasites are building a resistance to the main anti-malarial compound artemisinin. 

Research also has been done at Australia’s Burnet Institute, which neutralized a malaria parasite in a similar manner. That research also appears in the journal Nature