Plasmodium falciparum gametocytes modify the mechanical properties of their erythrocyte host to persist for several weeks in the blood circulation and to be available for mosquitoes. These changes are tightly regulated by the plasmodial phosphodiesterase delta that decreases both the stiffness and the permeability of the infected host cell. Here, we address the effect of the phosphodiesterase inhibitor tadalafil on deformability and permeability of gametocyte-infected erythrocytes. We show that this inhibitor drastically increases isosmotic lysis of gametocyte-infected erythrocytes and impairs their ability to circulate in an in vitro model for splenic retention. These findings indicate that tadalafil represents a novel drug lead potentially capable of blocking malaria parasite transmission by impacting gametocyte circulation.

恶性疟原虫配子体改变其红细胞宿主的机械特性，使其在血液循环中持续数周并可供蚊子使用。这些变化受到疟原虫磷酸二酯酶 delta 的严格调控，它会降低受感染宿主细胞的硬度和渗透性。在这里，我们解决了磷酸二酯酶抑制剂他达拉非对配子体感染红细胞的变形能力和渗透性的影响。我们表明，这种抑制剂显着增加了受配子体感染的红细胞的等渗裂解，并损害了它们在脾脏滞留的体外模型中循环的能力。这些发现表明，他达拉非代表了一种新的药物先导，可能能够通过影响配子体循环来阻断疟疾寄生虫的传播。