Researchers have discovered the proteins that enable a malaria parasite to make its way out of blood cells in order to infect other neighboring cells. The team studied Plasmodium falciparum, known to be the most deadly malaria parasite because it multiplies rapidly and has the ability to clog blood vessels, which can be fatal. The proteins identified in the study are potential drug targets for new malaria treatments. The paper describing the findings is published in Nature Microbiology.
It’s known that malaria parasites remain contained inside a vacuole in red blood cells while they replicate. They must first burst out of the vacuole then they are required to break through the red blood cell membrane in order to infect other cells. This new study used gene knockout technology to identify that a protein called SUB1 is required for the parasite to break out of the vacuole. Experiments showed that parasites with a knockout SUB1 gene were not capable of breaking out of the internal cellular compartment. The study also identified that an enzyme named SERA6 is required for the parasites to complete the second step in exiting the cell—breaking through the red blood cell membrane—and that SUB1 activates SERA6.
Further experiments demonstrated the mechanism by which SERA6 allows the parasite to puncture the cell membrane. PhD student at the Francis Crick Institute and joint first-author Michele Tan explains: "There is a strong chicken wire-like meshwork that sits under the red blood cell membrane to provide strength and support. We found that SERA6 cuts the chicken wire, causing the blood cell membrane to collapse and rip open so that the parasites can escape."
The research group has already started collaborating with GSK to investigate whether or not these two proteins can be viable targets for new anti-malarial drugs.
Image: "Ring forms" of the Plasmodium falciparum (malaria) parasite, inside red blood cells. Microscope image using 100x oil-immersion lens. From a blood smear, stained with hematoxylin. Image courtesy of MichaelZahniser, via Wikimedia Commons.