New stages in the program of malaria parasite egress imaged in normal and sickle erythrocytes.
The apicomplexan parasite Plasmodium falciparum causes malignant malaria. The mechanism of parasite egress from infected erythrocytes that disseminate parasites in the host at the end of each asexual cycle is unknown. Two new stages of the egress program are revealed: (1) swelling of the parasitophorous vacuole accompanied by shrinkage of the erythrocyte compartment, and (2) poration of the host cell membrane seconds before erythrocyte rupture because of egress. Egress was inhibited in dehydrated cells from patients with sickle cell disease in accord with experimental dehydration of normal cells, suggesting that vacuole swelling involves intake of water from the erythrocyte compartment. Erythrocyte membrane poration occurs in relaxed cells, thus excluding involvement of osmotic pressure in this process. Poration does not depend on cysteine protease activity, because protease inhibition blocks egress but not poration, and poration is required for the parasite cycle because the membrane sealant P1107 interferes with egress. We suggest the following egress program: parasites initiate water influx into the vacuole from the erythrocyte cytosol to expand the vacuole for parasite separation and vacuole rupture upon its critical swelling. Separated parasites leave the erythrocyte by breaching its membrane, weakened by putative digestion of erythrocyte cytoskeleton and membrane poration.
Glushakova
Svetlana
S
Program in Physical Biology, Eunice Kennedy Schriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Humphrey
Glen
G
Leikina
Evgenia
E
Balaban
Amanda
A
Miller
Jeffrey
J
Zimmerberg
Joshua
J
D000755:Anemia, Sickle Cell / Q000097:blood*; D000818:Animals; D001483:Base Sequence; D002462:Cell Membrane; D017931:DNA Primers; D004912:Erythrocytes / Q000469:parasitology*; D004913:Erythrocytes, Abnormal / Q000469:parasitology*; D006801:Humans; D010963:Plasmodium falciparum / Q000502:physiology*
D017931:DNA Primers