Malaria escape route reveals new drug target

Malarial parasites need a protein called MSP1 to burst from red blood cells to infect new cells. The discovery, made by researchers at the Francis Crick Institute, solves the long-held parasite escape puzzle and so reveals a new anti-malarial drug target.

A team led by Professor Mike Blackman of the Crick (currently based at Mill Hill) altered the genes of live parasites and then, using video microscopy, watched their attempts to break out of red blood cells.

Professor Blackman’s team found parasites without the MSP1 protein on their surface cannot attach to the inside rim of the red blood cell; the parasites are trapped.

They also uncovered the exact mechanism. MSP1 needs to be altered by an enzyme called SUB1 to stick to the red blood cell. Without the SUB1 enzyme the MSP1 protein cannot attach to the red cell membrane and ultimately the parasite can’t escape.

Professor Blackman said: “Malaria causes immense suffering and mortality across much of the developing world. New types of antimalarial drugs are urgently needed in the face of widespread resistance to most available drugs. Our work confirms the SUB1 enzyme in the malaria parasite is an important potential target.”

Time lapse video recorded by Blackman’s team shows malarial parasites with MSP1 breaking a hole in the red blood cell. The weakened cell wall then folds open like an envelope and the parasites rush out to infect more red blood cells. This destruction creates the fatal fever and anaemia typical of malaria.

Professor Blackman concludes: “Collectively, our findings change the way we think about how the malaria parasite escapes cells. We now know that mechanical forces exerted from the inside of the infected red blood cells are crucial. Interactions between MSP1 on the parasite and a protein called spectrin in the red blood cell wall ruptures the cell membrane and the parasite escapes.”

The paper, Processing of Plasmodium falciparum merozoite surface protein MSP1 activates a spectrin-binding function enabling parasite egress from RBCs, is published in Cell Host & Microbe. 

This time-lapse video shows normal malaria parasite escape from red blood cells (left-hand side) compared to a parasite lacking surface MSP1 (right-hand side). Parasites without MSP1 become trapped in the partially-ruptured red blood cell. © Professor Michael Blackman, The Francis Crick Institute.

  • Research from the Francis Crick Institute that solves the long-held malaria parasite escape puzzle has revealed a new anti-malarial drug target.
  • The work also involved collaborators from the University of Heidelberg, the Wellcome Trust Sanger Institute and Birkbeck College London.