Last week’s edition of Nature published some exciting advancements towards Malaria research. A laboratory in Australia, the Walter & Eliza Hall Institute of Medical Research, identified an essential protein needed by the malaria parasite for survival. Additionally, the Washington University School of Medicine in St Louis identified the same protein as being a potential vaccine target, which only further confirmed the findings in Australia.
Background While malaria can be caused from several different species of the protist Plasmodium, the most virulent form is caused by Plasmodium falciparum. When an individual is bitten by a malaria infected mosquito, the parasites are transmitted into the blood. The parasites enter the red blood cells (RBC) and immediately begin exporting hundreds of effector proteins (effectors bind to another protein thereby activating or inhibiting activity) into the RBC’s cytoplasm, in so doing the parasite alters their intracellular environment so as to evade an immune response, permitting their replication and spread of infection, thus ensuring survival.
Current Research The published research identifies a protein, Plasmepsin V, directly essential to the export of effector proteins into the cell. Plasmepsin V is a membrane-bound aspartic protease, which primes the effector proteins prior to export. It recognizes a particular “tag” on the proteins to be secreted and cleaves it off. The cleaved/primed protein is believed to bind to a chaperone protein which carries it to the membrane channel, where it is exported to the RBC’s intracellular space. In vitro assays demonstrated that by interfering with Plasmepsin V activity effector protein export is inhibited, thus preventing the spread of infection. Plasmepsin V makes for an excellent drug target for two reasons: its closest equivalent in humans is the very distantly related Beta Secretase, which would hopefully minimize any potential adverse side effects, and because this protein does not vary widely across the four different Plasmodium species.
Why is this significant?
Following information obtained from WHO World Malaria Report 2009
- half of the world’s population is at risk for malaria - an estimated 243 million cases occurred worldwide in 2008 - an estimated 863 thousand deaths occurred worldwide in 2008 - the damages of this disease continue to cripple any hope for economic development in Africa
Photo credit: WHO