October 30, 2017Tropical Disease
Plasmodium falciparum, the species of parasite that causes the most malaria deaths worldwide, has developed drug-resistance in five countries in Southeast Asia. According to an article published on line in Science (27 October 2017), this parasite needs two proteins to infect red blood cells and exit the cells after it multiplies, a finding that may provide new targets for drug development.
In the current study, the authors sought to uncover the role of plasmepsins IX and X, two of the 10 types of plasmepsin proteins produced by P. falciparum for metabolic and other processes. To do this, the authors created malaria parasites that lacked plasmepsin IX or X under experimental conditions and compared them to those that had the two proteins. The authors found plasmepsin IX in rhoptries, specialized cell structures inside the parasite, which help it invade red blood cells. Parasites lacking plasmepsin IX had defective rhoptries. In addition, the authors observed plasmepsin X in exonemes-small vesicles (balloon-like structures) that help malaria parasites exit infected cells. The authors also discovered that plasmepsin X processes an important protein called SUB1. When deprived of plasmepsin X, the parasites couldn't process SUB1 and couldn't infect red blood cells or exit these cells after multiplying.
The authors also identified three experimental malaria drugs that may work by targeting plasmepsin X. One drug, called CWHM-117, has already been tested in a mouse model of malaria. The new findings may help researchers modify CWHM-117 to make it more effective. Furthermore, parasites lacking the plasmepsins could potentially be used to screen candidate drugs to identify additional anti-malaria compounds.