Samuelson J C, Burke A, Courval J M
Department of Tropical Public Health, Harvard School of Public Health, Boston, Massachusetts 02115.
Antimicrob Agents Chemother. 1992 Nov;36(11):2392-7. doi: 10.1128/AAC.36.11.2392.
Previously a cloned emetine-resistant mutant of the protozoal parasite Entamoeba histolytica was shown to overexpress a gene for an ameba homolog of the mammalian P-glycoprotein, a plasma membrane pump that removes hydrophobic drugs from multidrug-resistant tumor cells. Three sets of experiments were performed to better characterize the multidrug-resistant phenotype of the emetine-resistant amebae. First, the emetine resistance of the mutant amebae was reversed by concentrations of calcium and sodium channel blockers effective in reversing drug resistance by multidrug-resistant tumor cells, but it was reversed only in the presence of very high concentrations of the tricyclic antidepressants. Second, the mutant amebae showed cross-resistance to antiamebic drugs used to treat luminal infection (iodoquinol and diloxanide) but were not cross-resistant to drugs used to treat invasive disease (chloroquine and metronidazole). Third, when amebae were loaded with radiolabeled emetine, the mutant parasites released the drug at approximately 1.6 times the rate of the wild-type organisms. We conclude that the emetine-resistant E. histolytica parasites have some but not all the features of the multidrug-resistant phenotype.
先前已表明，原生动物寄生虫溶组织内阿米巴的一种克隆的抗吐根碱突变体过表达一种与哺乳动物P-糖蛋白的阿米巴同源物的基因，P-糖蛋白是一种质膜泵，可从多药耐药肿瘤细胞中清除疏水性药物。进行了三组实验，以更好地表征抗吐根碱阿米巴的多药耐药表型。首先，突变阿米巴对吐根碱的抗性可被有效逆转多药耐药肿瘤细胞耐药性的钙通道阻滞剂和钠通道阻滞剂浓度所逆转，但仅在存在非常高浓度的三环类抗抑郁药时才被逆转。其次，突变阿米巴对用于治疗肠腔感染的抗阿米巴药物（碘喹啉和地洛酰胺）表现出交叉耐药性，但对用于治疗侵袭性疾病的药物（氯喹和甲硝唑）没有交叉耐药性。第三，当给阿米巴加载放射性标记的吐根碱时，突变寄生虫释放药物的速率约为野生型生物体的1.6倍。我们得出结论，抗吐根碱的溶组织内阿米巴寄生虫具有多药耐药表型的一些但并非全部特征。
