Hidden away in a human red blood cell, the malaria parasite evades the immune system. To grow properly, the parasite must obtain nutrients from the bloodstream. Infected cells are known to take up more nutrients than uninfected cells, but how this is achieved was not clear.
NIAID investigators have made important inroads toward solving this mystery by identifying an unusual ion channel on the red blood cell membrane of infected cells. The channel, known as the plasmodial surface anion channel (PSAC), forms tiny pores that allow small nutrient molecules and other solutes to move into and out of the cell. However, it was unclear whether PSAC is made by the parasite or is a human protein that was co-opted by the parasite.
The infected cell is in the center of the image. To the left are uninfected cells with a smooth red surface.
To answer this question, the scientists screened some 50,000 chemicals to find those that block nutrient uptake by PSAC. They screened four genetically distinct strains of malaria parasites and found a chemical that is highly specific for channels of a single strain, suggesting slightly different channels are made by each parasite. They then used genetic studies to find two related parasite genes that control PSAC activity. The protein made by these genes localizes to the red blood cell membrane and may by itself form PSAC.
The genes the researchers found are present in all malaria parasites but are absent from all other organisms. They are very different from channel genes in humans, suggesting that specific PSAC inhibitors can be developed into new and desperately needed antimalarial drugs. The NIAID team has already shown that PSAC inhibitors kill malaria parasites in laboratory cultures. The team is also exploring how the PSAC protein is transported from the parasite to the red blood cell membrane, as preventing this transport may be another way to kill the parasite and treat malaria.
Reference: Nguitragool W, Bokhari AA, Pillai AD, Rayavara K, Sharma P, Turpin B, Aravind L, Desai SA. Malaria parasite clag3 genes determine channel-mediated nutrient uptake by infected red blood cells. Cell. 2011 May 27;145(5):665-77.
Last Updated January 08, 2013
Last Reviewed January 08, 2013