Selective Inhibition of a Two-step Egress of Malaria Parasites from the Host Erythrocyte

Escape from the host erythrocyte by the invasive stage of the malaria parasite Plasmodium falciparum is a fundamental step in the pathogenesis of malaria of which little is known. Upon merozoite invasion of the host cell, the parasite becomes enclosed within a parasitophorous vacuole, the compartmen...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2003-09, Vol.278 (39), p.37658-37663
Main Authors: Wickham, Mark E., Culvenor, Janetta G., Cowman, Alan F.
Format: Article
Language:English
Subjects:
Animals
Antigens, Protozoan - physiology
Erythrocytes - parasitology
Green Fluorescent Proteins
Luminescent Proteins - genetics
Peptides - genetics
Peptides - physiology
Plasmodium falciparum - physiology
Protozoan Proteins
Vacuoles - parasitology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Escape from the host erythrocyte by the invasive stage of the malaria parasite Plasmodium falciparum is a fundamental step in the pathogenesis of malaria of which little is known. Upon merozoite invasion of the host cell, the parasite becomes enclosed within a parasitophorous vacuole, the compartment in which the parasite undergoes growth followed by asexual division to produce 16–32 daughter merozoites. These daughter cells are released upon parasitophorous vacuole and erythrocyte membrane rupture. To examine the process of merozoite release, we used P. falciparum lines expressing green fluorescent protein-chimeric proteins targeted to the compartments from which merozoites must exit: the parasitophorous vacuole and the host erythrocyte cytosol. This allowed visualization of merozoite release in live parasites. Herein we provide the first evidence in live, untreated cells that merozoite release involves a primary rupture of the parasitophorous vacuole membrane followed by a secondary rupture of the erythrocyte plasma membrane. We have confirmed, with the use of immunoelectron microscopy, that parasitophorous vacuole membrane rupture occurs before erythrocyte plasma membrane rupture in untransfected wild-type parasites. We have also demonstrated selective inhibition of each step in this two-step process of exit using different protease inhibitors, implicating the involvement of distinct proteases in each of these steps. This will facilitate the identification of the parasite and host molecules involved in merozoite release.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M305252200