To ensure the transport of nutrients necessary for their survival, Plasmodium falciparum parasites increase erythrocyte permeability to diverse solutes. These new permeation pathways (NPPs) have been extensively characterized in the pathogenic asexual parasite stages, however the existence of NPPs has never been investigated in gametocytes, the sexual stages responsible for transmission to mosquitoes. Here, we show that NPPs are still active in erythrocytes infected with immature gametocytes and that this activity declines along gametocyte maturation. Our results indicate that NPPs are regulated by cyclic AMP (cAMP) signaling cascade, and that the decrease in cAMP levels in mature stages results in a slowdown of NPP activity. We also show that NPPs facilitate the uptake of artemisinin derivatives and that phosphodiesterase (PDE) inhibitors can reactivate NPPs and increase drug uptake in mature gametocytes. These processes are predicted to play a key role in P. falciparum gametocyte biology and susceptibility to antimalarials.

为了确保其生存所需的营养物质的运输，恶性疟原虫寄生虫增加红细胞对不同溶质的渗透性。这些新的渗透途径 (NPP) 已在致病性无性寄生虫阶段得到广泛表征，但从未在配子体中研究过 NPP 的存在，而配子体是负责传播给蚊子的有性阶段。在这里，我们表明 NPPs 在感染了未成熟配子体的红细胞中仍然活跃，并且这种活性随着配子体成熟而下降。我们的结果表明 NPP 受环 AMP (cAMP) 信号级联调节，并且成熟阶段 cAMP 水平的降低导致 NPP 活性减慢。我们还表明 NPPs 促进青蒿素衍生物的吸收，磷酸二酯酶 (PDE) 抑制剂可以重新激活 NPPs 并增加成熟配子细胞的药物吸收。恶性疟原虫配子体生物学和对抗疟药的敏感性。