The lifecycle of all Plasmodium species is complex and involves a round of replication in host erythrocytes. The clinical manifestations of malaria are linked to this stage in the lifecycle and are associated with rupture of the infected erythrocytes. During this growth phase, the parasite enters the erythrocyte and then releases several hundred effector proteins into the cytoplasm. These key virulence proteins provide a suitable environment for multiplication and allow the parasite to evade the host immune system. Proteins destined for export contain a conserved pentameric motif known as PEXEL and, when this is cleaved in the endoplasmic reticulum, the protein can be transported into the host cell. Two independent studies by scientists in the US and Australia have now shown that the protease responsible for cleaving the PEXEL motif is the aspartyl protease, plasmepsin V. Cleavage reveals an export signal at the amino terminus of the cargo protein which is then transported into the host cell cytoplasm, likely through a channel in the parasite’s outer membrane. Since export of the effector proteins is essential for the erythrocytic stage of the plasmodium life-cycle, drugs that block plasmepsin V should provide an effective treatment for malaria.
Both studies are published in the journal Nature (Australian study; US study).
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I published a paper entitled “Identification onitor (2010), volumen 19(3), pp. 15-19 Available at http://www.finlay.sld.cu/publicaciones/vaccimonitor/Vm2010/a14.pdf.
Abstract: In this paper, we suggested eleven protein targets to be used as possible vaccines against Plasmodium falciparum causative agent of almost two to three million deaths per year. A comprehensive analysis of protein target have been selected from the small experimental fragment of antigen in the P. falciparum genome, all of them common to the four stages of the parasite life cycle (i.e., sporozoites, merozoites, trophozoites and gametocytes). The potential vaccine candidates should be analyzed in silico technique using various bioinformatics tools. Finally, the possible protein target according to PlasmoDB gene ID are PFC0975c, PFE0660c, PF08_0071, PF10_0084, PFI0180w, MAL13P1.56, PF14_0192, PF13_0141, PF14_0425, PF13_0322, y PF14_0598.