Malaria_1

Malaria parasites live inside red blood cells, feeding on proteins and breaking them down so that they can use the proceeds (amino acids) as building blocks for their own proteins. When they have reached a sufficient size they divide and burst out of the red cell and enter another, repeating the process until severe disease or death occurs. Above, the malaria plasmodium. (Courtesy: Public Library of Science journal/Wikimedia Commons)

MCGILL (CAN)—A multinational team may have identified a target for a new malaria treatment by disabling digestive enzymes in malaria parasites, which are transmitted by mosquito bites.

The parasites live inside red blood cells, feeding on proteins and breaking them down so that they can use the proceeds (amino acids) as building blocks for their own proteins. When they have reached a sufficient size they divide and burst out of the red cell and enter another, repeating the process until severe disease or death occurs.

John Dalton, a biochemist in McGill University, and his colleagues found that certain digestive enzymes in the parasites enable them to undertake this process. Importantly, the researchers have also now determined the three-dimensional structures of two enzymes and demonstrated how drugs can be designed to disable them.

“By blocking the action of these critical parasite enzymes, we have shown that the parasites can no longer survive within the human red blood cell,” Dalton explains.

The team is putting their findings into action immediately and is already pursuing anti-malarial drug development. Details of the work are reported in the Proceedings of the National Academy of Sciences.

His recent findings build on earlier work in which he examined worm parasites Schistosoma mansoni (also known as “blood fluke”) and F. hepatica (“liver fluke”). 200 million people are infected every year with these worm parasites, of whom 20,000 to 80,000 will eventually die. Living in lakes and waterways, they are able to recognize human skin and burrow through into the blood stream.

Dalton and his colleagues in Ireland and Australia discovered that the worm parasites are able to shut-off the body’s pro-inflammatory response by releasing proteases (a kind of enzyme) once in the blood stream. Macrophages, the white blood cells that would normally provoke a pro-inflammatory response, take up the proteases. Once inside the macrophage the protease switches off key cellular signals. This enables the parasite to survive and reproduce in the host for years, even decades.

The multinational team includes researchers from Australia’s Queensland Institute of Medical Research, Monash University and the University of Western Sydney, Wroclaw University of Technology in Poland, and the University of Virginia.

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