Ullman B
Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland 97201-3098, USA.
J Bioenerg Biomembr. 1995 Feb;27(1):77-84. doi: 10.1007/BF02110334.
Drug resistance has emerged as a devasting impediment to the treatment and control of diseases of parasitic origin. The underlying mechanisms that contribute to this drug resistance in field isolates, however, are poorly understood. Members of the P-glycoprotein gene (pgp) family have been identified, cloned, and sequenced in Plasmodia, Leishmania, and Entamoeba, and variations in pgp copy number and/or expression have been implicated as a basis for drug resistance in each of these genera. The spectrum of drugs to which parasitic protozoa containing amplified pgp genes and/or transcripts are refractory range from a phenotype similar to that observed with multidrug-resistant mammalian cells to those that are completely distinct. The availability of molecular probes to pgp genes provides valuable reagents to dissect the role of pgp gene amplification and overexpression in mediating drug resistance in parasitic protozoa and to determine the physiological function of P-glycoproteins in this clinically consequential group of human pathogens.
耐药性已成为治疗和控制寄生虫源性疾病的巨大障碍。然而，对于野外分离株中导致这种耐药性的潜在机制，我们了解甚少。P-糖蛋白基因（pgp）家族的成员已在疟原虫、利什曼原虫和内阿米巴中得到鉴定、克隆和测序，并且pgp拷贝数和/或表达的变化被认为是这些属中耐药性的基础。含有扩增的pgp基因和/或转录本的寄生原生动物对药物产生耐药的范围很广，从类似于多药耐药哺乳动物细胞所观察到的表型到完全不同的表型。用于pgp基因的分子探针的可用性提供了有价值的试剂，可用于剖析pgp基因扩增和过表达在介导寄生原生动物耐药性中的作用，并确定P-糖蛋白在这一具有临床重要性的人类病原体群体中的生理功能。
