Membrane transport proteins, also known as transporters, control the movement of ions, nutrients, metabolites, and waste products across the membranes of a cell and are central to its biology. Proteins of this type also serve as drug targets and are key players in the phenomenon of drug resistance. The malaria parasite has a relatively reduced transportome, with only approximately 2.5% of its genes encoding transporters. Even so, assigning functions and physiological roles to these proteins, and ascertaining their contributions to drug action and drug resistance, has been very challenging. This review presents a detailed critique and synthesis of the disruption phenotypes, protein subcellular localisations, protein functions (observed or predicted), and links to antimalarial drug resistance for each of the parasite's transporter genes. The breadth and depth of the gene disruption data are particularly impressive, with at least one phenotype determined in the parasite's asexual blood stage for each transporter gene, and multiple phenotypes available for 76% of the genes. Analysis of the curated data set revealed there to be relatively little redundancy in the Plasmodium transportome; almost two‐thirds of the parasite's transporter genes are essential or required for normal growth in the asexual blood stage of the parasite, and this proportion increased to 78% when the disruption phenotypes available for the other parasite life stages were included in the analysis. These observations, together with the finding that 22% of the transportome is implicated in the parasite's resistance to existing antimalarials and/or drugs within the development pipeline, indicate that transporters are likely to serve, or are already serving, as drug targets. Integration of the different biological and bioinformatic data sets also enabled the selection of candidates for transport processes known to be essential for parasite survival, but for which the underlying proteins have thus far remained undiscovered. These include potential transporters of pantothenate, isoleucine, or isopentenyl diphosphate, as well as putative anion‐selective channels that may serve as the pore component of the parasite's ‘new permeation pathways’. Other novel insights into the parasite's biology included the identification of transporters for the potential development of antimalarial treatments, transmission‐blocking drugs, prophylactics, and genetically attenuated vaccines. The syntheses presented herein set a foundation for elucidating the functions and physiological roles of key members of the Plasmodium transportome and, ultimately, to explore and realise their potential as therapeutic targets.

中文翻译：

---

疟原虫的转运体

膜转运蛋白，也称为转运蛋白，控制离子、营养物质、代谢物和废物穿过细胞膜的运动，是其生物学的核心。这种类型的蛋白质也可作为药物靶点，并且是耐药现象的关键参与者。疟原虫的转运体相对减少，只有大约 2.5% 的基因编码转运蛋白。即便如此，为这些蛋白质分配功能和生理作用，并确定它们对药物作用和耐药性的贡献，一直非常具有挑战性。这篇综述对破坏表型、蛋白质亚细胞定位、蛋白质功能（观察或预测）以及与每个寄生虫转运蛋白基因的抗疟药物耐药性的联系进行了详细的批评和综合。基因破坏数据的广度和深度尤其令人印象深刻，每个转运蛋白基因在寄生虫的无性血阶段至少确定了一种表型，而 76% 的基因有多种表型可用。对精选数据集的分析显示，疟原虫转运组中的冗余相对较少；在寄生虫的无性血阶段，几乎三分之二的寄生虫转运基因是正常生长所必需的或必需的，当分析中包括其他寄生虫生命阶段可用的破坏表型时，这一比例增加到 78%。这些观察结果，以及 22% 的转运体与寄生虫对开发管道中现有抗疟药和/或药物的抗性有关的发现，表明转运蛋白可能或已经作为药物靶点。不同生物和生物信息学数据集的整合也使得能够选择已知对寄生虫生存至关重要的运输过程的候选者，但迄今为止，其潜在蛋白质仍未被发现。这些包括泛酸、异亮氨酸或异戊烯基二磷酸的潜在转运蛋白，以及可能作为寄生虫“新渗透途径”的孔隙成分的假定阴离子选择性通道。对寄生虫生物学的其他新见解包括识别转运蛋白，用于抗疟治疗、传播阻断药物、预防剂和基因减毒疫苗的潜在发展。