Staines Henry M, Moore Cathy M, Slavic Ksenija, Krishna Sanjeev
Institute for Infection and Immunity, St George's University of London, Cranmer Terrace, London SW17 0RE, U.K.
Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, Lisbon 1649-028, Portugal.
Emerg Top Life Sci. 2017 Dec 22;1(6):553-561. doi: 10.1042/ETLS20170097.
Apicomplexa are a large group of eukaryotic, single-celled parasites, with complex life cycles that occur within a wide range of different microenvironments. They include important human pathogens such as Plasmodium, the causal agent of malaria, and Toxoplasma, which causes toxoplasmosis most often in immunocompromised individuals. Despite environmental differences in their life cycles, these parasites retain the ability to obtain nutrients, remove waste products, and control ion balances. They achieve this flexibility by relying on proteins that can deliver and remove solutes. This reliance on transport proteins for essential functions makes these pathways excellent potential targets for drug development programmes. Transport proteins are frequently key mediators of drug resistance by their ability to remove drugs from their sites of action. The study of transport processes mediated by integral membrane proteins and, in particular, identification of their physiological functions and localisation, and differentiation from host orthologues has already established new validated drug targets. Our understanding of how apicomplexan parasites have adapted to changing environmental challenges has also increased through the study of their transporters. This brief introduction to membrane transporters of apicomplexans highlights recent discoveries focusing on Plasmodium and emphasises future directions.
顶复门原虫是一大类真核单细胞寄生虫,具有复杂的生命周期,可在多种不同的微环境中出现。它们包括重要的人类病原体,如疟疾的病原体疟原虫,以及弓形虫,弓形虫最常在免疫功能低下的个体中引起弓形虫病。尽管它们生命周期中的环境存在差异,但这些寄生虫仍具备获取营养、清除废物和控制离子平衡的能力。它们通过依赖能够转运和清除溶质的蛋白质来实现这种灵活性。对基本功能依赖转运蛋白使得这些途径成为药物研发项目极具潜力的靶点。转运蛋白常常因其能够将药物从作用位点清除而成为耐药性的关键介导因素。对由整合膜蛋白介导的转运过程的研究,尤其是对其生理功能和定位的鉴定,以及与宿主同源物的区分,已经确立了新的经过验证的药物靶点。通过对其转运体的研究,我们对顶复门寄生虫如何适应不断变化的环境挑战的理解也有所增加。本文对顶复门原虫膜转运体的简要介绍突出了近期以疟原虫为重点的发现,并强调了未来的研究方向。