大多数多药物抗药性机理(对抗生素、抗菌剂、抗疟疾药物、杀虫剂，还有对人类的癌症化疗药物等多种药物的抗药性)涉及一种能够将药物抽出细胞的转运蛋白。研究人员对这种转运蛋白的原型分子——哺乳动物P-糖蛋白——几十年来已经作了大量研究，但只是在过去几年里才获得了充分的结构和生化数据，使我们能够从机理上对其有一个认识。Chris Higgins对我们当前关于4大类多药物转运蛋白的知识进行了综述。这4类转运蛋白之间的不同之处和相似之处正在为了解多药物抗药性是怎样实现的提供新的线索。这项工作尚未解决紧迫的临床问题，但也许能够为制定防止或绕过多药物抗药性的策略铺平道路。
Review
Nature 446, 749-757 (12 April 2007) | doi:10.1038/nature05630
Multiple molecular mechanisms for multidrug resistance transporters
Christopher F. Higgins1,2
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The acquisition of multidrug resistance is a serious impediment to improved healthcare. Multidrug resistance is most frequently due to active transporters that pump a broad spectrum of chemically distinct, cytotoxic molecules out of cells, including antibiotics, antimalarials, herbicides and cancer chemotherapeutics in humans. The paradigm multidrug transporter, mammalian P-glycoprotein, was identified 30 years ago. Nonetheless, success in overcoming or circumventing multidrug resistance in a clinical setting has been modest. Recent structural and biochemical data for several multidrug transporters now provide mechanistic insights into how they work. Organisms have evolved several elegant solutions to ridding the cell of such cytotoxic compounds. Answers are emerging to questions such as how multispecificity for different drugs is achieved, why multidrug resistance arises so readily, and what chance there is of devising a clinical solution.
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MRC Clinical Sciences Centre, Imperial College, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK
Present Address: Vice-Chancellor's Office, Durham University, The University Offices, Old Elvet, Durham DH1 3HP, UK.
Correspondence to: Christopher F. Higgins1,2 Correspondence should be addressed to the author (Email: chris.higgins@durham.ac.uk).
