Gómez M D, Pérez D G, Ayala P, Samuelson J, Orozco E
Departamento de Patología Experimental, Centro de Investigación y de Estudios Avanzados del I.P.N., México, D.F.
Arch Med Res. 1996 Autumn;27(3):421-5.
In this paper, we present the most relevant facts on multidrug resistance (MDR) in the protozoan parasite Entamoeba histolytica. MDR in E. histolytica presents characteristics similar to transformed mammalian cells. E. histolytica drug resistant mutants show cross-resistance to several drugs, and as in mammalian cells the resistance is reverted by verapamil. Six P-glycoprotein-like genes (EhPgp) have been cloned and characterized. Apparently, four of these genes are transcribed in drug-resistant mutants (EhPgp1, EhPgp2, EhPgp5 and EhPgp6), although only EhPgp1, EhPgp5 and EhPgp6 transcripts were clearly detected. The open reading frame (ORF) of the four completely full length genes is about 1300 amino acids long. EhPgp1, EhPgp2 and EhPgp5 have between 64 and 67% of positional identity among them, while EhPgp6 shows 38 to 46% positional identity to the other ameba genes. Interestingly, the phylogenetic tree suggested that Entamoeba P-glycoproteins are more related to the human and mouse P-glycoproteins than to the Plasmodium and Leishmania P-glycoproteins. Differential gene expression in drug-resistant mutants was detected when specific probes for each Ehpgp gene were used. To understand the differential expression of EhPgp genes we initiated the characterization of the upstream flanking regions of EhPgp1 and EhPgp5 genes. Upstream sequences showed between 53 and 66% of positional identity to Dictyostelium discoideum promoters.
在本文中，我们介绍了原生动物寄生虫溶组织内阿米巴中多药耐药性（MDR）的最相关事实。溶组织内阿米巴的多药耐药性呈现出与转化哺乳动物细胞相似的特征。溶组织内阿米巴耐药突变体对多种药物表现出交叉耐药性，并且与哺乳动物细胞一样，维拉帕米可逆转这种耐药性。已克隆并鉴定了六个P-糖蛋白样基因（EhPgp）。显然，其中四个基因在耐药突变体中被转录（EhPgp1、EhPgp2、EhPgp5和EhPgp6），尽管仅清晰检测到EhPgp1、EhPgp5和EhPgp6的转录本。四个全长完整基因的开放阅读框（ORF）约有1300个氨基酸长。EhPgp1、EhPgp2和EhPgp5之间的位置同一性为64%至67%，而EhPgp6与其他阿米巴基因的位置同一性为38%至46%。有趣的是，系统发育树表明，与疟原虫和利什曼原虫的P-糖蛋白相比，溶组织内阿米巴的P-糖蛋白与人类和小鼠的P-糖蛋白关系更为密切。当使用针对每个Ehpgp基因的特异性探针时，在耐药突变体中检测到了差异基因表达。为了了解EhPgp基因的差异表达，我们开始对EhPgp1和EhPgp5基因的上游侧翼区域进行表征。上游序列与盘基网柄菌启动子的位置同一性为53%至66%。
