New target for anti-malaria drugs
Malaria parasites must invade the erythrocytes of the host to be able to grow and multiply. Having depleted the host cell of its nutrients, the parasites break out to invade new erythrocytes. Researchers have discovered that a new organelle, the exoneme, which contains a protease SUB1, helps the parasite to escape from old erythrocytes and invade new ones. By scanning thousands of compounds, the researchers also found a plant-derived molecule that was able to block the SUB1 enzyme preventing the merozoites from escaping.
Subcellular Discharge of a Serine Protease Mediates Release of Invasive Malaria Parasites from Host Erythrocytes
Cell 2007 131: 1072-1083
The most virulent form of malaria is caused by waves of replication of blood stages of the protozoan pathogen Plasmodium falciparum. The parasite divides within an intraerythrocytic parasitophorous vacuole until rupture of the vacuole and host-cell membranes releases merozoites that invade fresh erythrocytes to repeat the cycle. Despite the importance of merozoite egress for disease progression, none of the molecular factors involved are known. Just prior to egress, an essential serine protease called PfSUB1 is discharged from previously unrecognized parasite organelles (termed exonemes) into the parasitophorous vacuole space. There, PfSUB1 mediates the proteolytic maturation of at least two essential members of another enzyme family called SERA. Pharmacological blockade of PfSUB1 inhibits egress and ablates the invasive capacity of released merozoites. Our findings reveal the presence in the malarial parasitophorous vacuole of a regulated, PfSUB1-mediated proteolytic processing event required for release of viable parasites from the host erythrocyte.
Related:
- Blood group O protects against severe malaria
- Malaria: now you see me, now you don’t
- Tough Choices – DDT or Malaria?
Tags: Biology, Health, Malaria, Medicine, Microbiology, Parasitology, Science
serpins or serine protease inhibitors are already available in the market. Lets hope the new discovery gives us the license to kill the rogues without doing least harm to the host systems.