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恶性疟原虫的耐药性与P-糖蛋白同源物

Drug resistance and the P-glycoprotein homologues of Plasmodium falciparum.

作者信息

Cowman A F, Karcz S

机构信息

Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.

出版信息

Semin Cell Biol. 1993 Feb;4(1):29-35. doi: 10.1006/scel.1993.1004.

DOI:10.1006/scel.1993.1004
PMID:8095826
Abstract

The chloroquine resistance phenotype of Plasmodium falciparum shares many similarities to multi-drug resistance in tumour cells and this has led to the identification of two mdr-like genes (pfmdr1, pfmdr2) from this human pathogen. The pfmdr1 gene has been linked to the chloroquine resistance phenotype, although a genetic cross appears to contradict these results. Analysis of drug resistant mutants selected in vitro has shown that the level of expression of the pfmdr1 gene can affect resistance to chloroquine, mefloquine, halofantrine and quinine. Mefloquine isolates from the field appear to always contain amplified levels of the pfmdr1 gene and also overexpress the transcript. They are also resistant to halofantrine suggesting a true multi-drug resistant phenotype.

摘要

恶性疟原虫的氯喹抗性表型与肿瘤细胞中的多药耐药性有许多相似之处,这使得人们从这种人类病原体中鉴定出了两个类似多药耐药的基因(pfmdr1、pfmdr2)。尽管遗传杂交似乎与这些结果相矛盾,但pfmdr1基因已与氯喹抗性表型相关联。对体外选择的耐药突变体的分析表明,pfmdr1基因的表达水平可影响对氯喹、甲氟喹、卤泛群和奎宁的抗性。从野外分离得到的甲氟喹菌株似乎总是含有扩增的pfmdr1基因水平,并且转录本也过度表达。它们对卤泛群也有抗性,提示存在真正的多药耐药表型。

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1
Drug resistance and the P-glycoprotein homologues of Plasmodium falciparum.恶性疟原虫的耐药性与P-糖蛋白同源物
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2
A strong association between mefloquine and halofantrine resistance and amplification, overexpression, and mutation in the P-glycoprotein gene homolog (pfmdr) of Plasmodium falciparum in vitro.甲氟喹与卤泛群耐药性以及恶性疟原虫P-糖蛋白基因同源物(pfmdr)的扩增、过表达和突变在体外存在强烈关联。
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Selection for high-level chloroquine resistance results in deamplification of the pfmdr1 gene and increased sensitivity to mefloquine in Plasmodium falciparum.对高水平氯喹耐药性的选择导致恶性疟原虫中pfmdr1基因的去扩增,并增加对甲氟喹的敏感性。
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