Wiser Mark F
Department of Tropical Medicine and Infectious Disease, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112-2824, USA.
Pathogens. 2024 Feb 20;13(3):182. doi: 10.3390/pathogens13030182.
The malaria parasite resides within erythrocytes during one stage of its life cycle. During this intraerythrocytic period, the parasite ingests the erythrocyte cytoplasm and digests approximately two-thirds of the host cell hemoglobin. This digestion occurs within a lysosome-like organelle called the digestive vacuole. Several proteases are localized to the digestive vacuole and these proteases sequentially breakdown hemoglobin into small peptides, dipeptides, and amino acids. The peptides are exported into the host cytoplasm via the chloroquine-resistance transporter and an amino acid transporter has also been identified on the digestive vacuole membrane. The environment of the digestive vacuole also provides appropriate conditions for the biocrystallization of toxic heme into non-toxic hemozoin by a poorly understood process. Hemozoin formation is an attribute of and and is not exhibited by other intraerythrocytic protozoan parasites. The efficient degradation of hemoglobin and detoxification of heme likely plays a major role in the high level of replication exhibited by malaria parasites within erythrocytes. Unique features of the digestive vacuole and the critical importance of nutrient acquisition provide therapeutic targets for the treatment of malaria.
疟原虫在其生命周期的一个阶段寄生于红细胞内。在这个红细胞内期,疟原虫摄取红细胞细胞质并消化大约三分之二的宿主细胞血红蛋白。这种消化发生在一种称为消化泡的溶酶体样细胞器内。几种蛋白酶定位于消化泡,这些蛋白酶将血红蛋白依次分解为小肽、二肽和氨基酸。这些肽通过氯喹抗性转运蛋白输出到宿主细胞质中,并且在消化泡膜上也鉴定出了一种氨基酸转运蛋白。消化泡的环境还通过一个了解甚少的过程为有毒血红素生物结晶为无毒疟色素提供了合适的条件。疟色素的形成是疟原虫和其他疟原虫的一个特征,其他红细胞内原生动物寄生虫则不表现出这种特征。血红蛋白的有效降解和血红素的解毒可能在疟原虫在红细胞内的高水平复制中起主要作用。消化泡的独特特征以及营养获取的关键重要性为疟疾治疗提供了治疗靶点。