Intraerythrocytic malaria parasites proliferate bounded by a parasitophorous vacuolar membrane (PVM). The PVM contains nutrient permeable channels (NPCs) conductive to small molecules, but their relevance for parasite growth for individual metabolites is largely untested. Here we show that growth-relevant levels of major carbon and energy sources pass through the NPCs. Moreover, we find that NPCs are a gate for several antimalarial drugs, highlighting their permeability properties as a critical factor for drug design. Looking into NPC-dependent amino acid transport, we find that amino acid shortage is a reason for the fitness cost in artemisinin-resistant (ART^R) parasites and provide evidence that NPC upregulation to increase amino acids acquisition is a mechanism of ART^R parasites in vitro and in human infections to compensate this fitness cost. Hence, the NPCs are important for nutrient and drug access and reveal amino acid deprivation as a critical constraint in ART^R parasites.

红细胞内疟原虫以寄生液泡膜 (PVM) 为界增殖。PVM 包含可传导小分子的营养渗透通道 (NPC)，但它们与单个代谢物的寄生虫生长的相关性在很大程度上未经测试。在这里，我们展示了与增长相关的主要碳和能源水平通过 NPC。此外，我们发现 NPC 是几种抗疟疾药物的大门，突出了它们的渗透性特性是药物设计的关键因素。研究 NPC 依赖性氨基酸转运，我们发现氨基酸短缺是青蒿素抗性 (ART ^R ) 寄生虫适应性成本的一个原因，并提供证据表明 NPC 上调以增加氨基酸获取是 ART ^R寄生虫的一种机制在体外和人类感染中，以补偿这种健身成本。因此，NPCs 对于营养和药物的获取很重要，并揭示了氨基酸剥夺是 ART ^R寄生虫的关键限制因素。