New drug targets for malaria found

Scientists have discovered crucial new processes that allow malaria parasites to escape red blood cells and infect other cells, offering potential new treatment targets.
The researchers are working with pharmaceutical companies to use this knowledge to develop new antimalarial drugs - a critical step in the battle against drug-resistant malaria.
"Over 400,000 people die of malaria each year, and resistance to common antimalarial drugs is growing," said Mike Blackman, professor at the Francis Crick Institute in the UK.
"We're studying the deadliest malaria parasite, Plasmodium falciparum, to try to find new drug targets that work in a different way to existing treatments," said Blackman, who led the study published in the journal Nature Microbiology.

The team identified two key proteins that malaria parasites need to escape red blood cells and infect fresh cells.
"We have already started collaborating with GSK to see if designing drugs that target these proteins could form the basis of a new antimalarial drug," said James Thomas, postdoctoral scholar at Crick.

When malaria parasites invade red blood cells, they form an internal compartment where they replicate many times before bursting out of the cell and infecting more cells.
In order to escape red blood cells, the parasites have to break through both the internal compartment and the red cell membrane.

The team used genetic knockout experiments to show that a protein called SUB1 is essential for the parasite to breakthrough the internal compartment.
Another protein SERA6 - which is activated by SUB1 - is essential for the parasite to break through the red blood cell membrane.
Using analytical tools, the team then figured out how SERA6 breaks through the blood cell membrane.
"There is a strong chicken wire-like meshwork that sits under the red blood cell membrane to provide strength and support," said Michele Tan, a PhD student at Crick.
"We found that SERA6 cuts the chicken wire, causing the blood cell membrane to collapse and rip open so that the parasites can escape," said Tan.