Peel S A
Department of Molecular Diagnostics and Pathogenesis, Division of Retrovirology Walter Reed Army Institute of Research, Rockville, MD, USA.
Drug Resist Updat. 2001 Feb;4(1):66-74. doi: 10.1054/drup.2001.0183.
The seminal observations that (a) chloroquine-resistant Plasmodium falciparum strains accumulate less drug than more sensitive parasites, and (b) chloroquine resistance could be modulated in vitro by the classic multidrug-resistance (MDR) modulator verapamil, suggested not only that parasite resistance to multiple drugs may be similar to the MDR phenotype described in mammalian cancer cells, but that homologous proteins may be involved. These findings prompted search for MDR-like genes in the parasite. To date, three full-length ABC transporter genes have been isolated from P. falciparum: two P-glycoprotein-like homologues, pfmdr1 and pfmdr2, and a homologue of the yeast GCN20 gene, pfgcn20.
(a)与更敏感的疟原虫相比,对氯喹耐药的恶性疟原虫菌株积累的药物更少;(b)经典的多药耐药(MDR)调节剂维拉帕米在体外可调节氯喹耐药性。这不仅表明寄生虫对多种药物的耐药性可能与哺乳动物癌细胞中描述的MDR表型相似,而且可能涉及同源蛋白。这些发现促使人们在寄生虫中寻找类MDR基因。迄今为止,已从恶性疟原虫中分离出三个全长ABC转运蛋白基因:两个类P-糖蛋白同源物,即pfmdr1和pfmdr2,以及酵母GCN20基因的一个同源物pfgcn20。