Program in Physical Biology, Eunice Kennedy Schriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Curr Biol. 2010 Jun 22;20(12):1117-21. doi: 10.1016/j.cub.2010.04.051. Epub 2010 May 27.
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.
疟原虫属寄生虫恶性疟原虫可引起恶性疟疾。寄生虫从受感染的红细胞中逸出并在每个无性周期结束时将寄生虫传播到宿主中的机制尚不清楚。现在揭示了逸出计划的两个新阶段：（1）滋养液泡肿胀，同时红细胞隔室收缩；（2）在红细胞破裂前几秒钟宿主细胞膜穿孔，因为逸出。与正常细胞的实验性脱水一致，镰状细胞病患者的脱水细胞中的逸出被抑制，这表明液泡肿胀涉及从红细胞隔室摄取水分。红细胞膜穿孔发生在松弛的细胞中，因此排除了渗透压在这个过程中的参与。穿孔不依赖半胱氨酸蛋白酶活性，因为蛋白酶抑制剂阻断逸出但不阻断穿孔，并且穿孔是寄生虫周期所必需的，因为膜密封剂 P1107 干扰逸出。我们提出以下逸出计划：寄生虫从红细胞细胞质开始将水吸入液泡中，以在液泡临界肿胀时扩大液泡以进行寄生虫分离和液泡破裂。分离的寄生虫通过破坏其膜离开红细胞，这是通过对红细胞细胞骨架和膜穿孔的推测性消化来削弱的。
