Cytoplasmic free Ca 2+ is essential for multiple steps in malaria parasite egress from infected erythrocytes

• Published in: Malaria Journal
• Main Authors: Glushakova Svetlana, Lizunov Vladimir, Blank Paul S, Melikov Kamran, Humphrey Glen, Zimmerberg Joshua
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2013
• Subjects: Plasmodium falciparum; Asexual cycle of replication; Parasite egress; Free calcium; Swelling of parasitophorous vacuole; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/1475-2875-12-41; https://doaj.org/article/052407c118844f7b90bfad1333b9a876

Abstract Background Egress of Plasmodium falciparum, from erythrocytes at the end of its asexual cycle and subsequent parasite invasion into new host cells, is responsible for parasite dissemination in the human body. The egress pathway is emerging as a coordinated multistep programme that extends in time for tens of minutes, ending with rapid parasite extrusion from erythrocytes. While the Ca 2+ regulation of the invasion of P. falciparum in erythrocytes is well established, the role of Ca 2+ in parasite egress is poorly understood. This study analysed the involvement of cytoplasmic free Ca 2+ in infected erythrocytes during the multistep egress programme of malaria parasites. Methods Live-cell fluorescence microscopy was used to image parasite egress from infected erythrocytes, assessing the effect of drugs modulating Ca 2+ homeostasis on the egress programme. Results A steady increase in cytoplasmic free Ca 2+ is found to precede parasite egress. This increase is independent of extracellular Ca 2+ for at least the last two hours of the cycle, but is dependent upon Ca 2+ release from internal stores. Intracellular BAPTA chelation of Ca 2+ within the last 45 minutes of the cycle inhibits egress prior to parasitophorous vacuole swelling and erythrocyte membrane poration, two characteristic morphological transformations preceding parasite egress. Inhibitors of the parasite endoplasmic reticulum (ER) Ca 2+ -ATPase accelerate parasite egress, indicating that Ca 2+ stores within the ER are sufficient in supporting egress. Markedly accelerated egress of apparently viable parasites was achieved in mature schizonts using Ca 2+ ionophore A23187. Ionophore treatment overcomes the BAPTA-induced block of parasite egress, confirming that free Ca 2+ is essential in egress initiation. Ionophore treatment of immature schizonts had an adverse effect inducing parasitophorous vacuole swelling and killing the parasites within the host cell. Conclusions The parasite egress programme requires intracellular free Ca 2+ for egress ...