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耐甲氟喹恶性疟原虫的基因组分析。

Genomic analysis of mefloquine-resistant Plasmodium falciparum.

作者信息

Begum Khurshida, Kim Hye-Sook, Okuda Yohei, Wataya Yusuke, Kimura Mikio, Huruta Takahisa

机构信息

Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan.

出版信息

Nucleic Acids Res Suppl. 2002(2):223-4. doi: 10.1093/nass/2.1.223.

DOI:10.1093/nass/2.1.223
PMID:12903186
Abstract

We studied sequence polymorphism, expression level of pfmdr1 gene and drug sensitivity in mefloquine sensitive-strain as well as mefloquine-resistant clone/24 to understand underlying drug resistance mechanism. Mefloquine-resistant clone/24 exhibited decreased susceptibility to mefloquine, quinine, halofantrine and artemisinin and increased susceptibility to chloroquine. We analyzed sequence of pfmdr1 gene and found mutation in pfmdr1 on clone/24. Moreover, overexpression of mRNA level of pfmdr1 has been observed in mefloquine-resistant clone/24. Our results explain gene mutation and expression level of pfmdr1 may be associated in mefloquine resistance mechanism.

摘要

我们研究了甲氟喹敏感株以及甲氟喹耐药克隆/24中的序列多态性、pfmdr1基因的表达水平和药物敏感性,以了解潜在的耐药机制。甲氟喹耐药克隆/24对甲氟喹、奎宁、卤泛群和青蒿素的敏感性降低,而对氯喹的敏感性增加。我们分析了pfmdr1基因的序列,发现在克隆/24的pfmdr1上存在突变。此外,在甲氟喹耐药克隆/24中观察到pfmdr1的mRNA水平过表达。我们的结果表明,pfmdr1的基因突变和表达水平可能与甲氟喹耐药机制有关。

相似文献

1
Genomic analysis of mefloquine-resistant Plasmodium falciparum.耐甲氟喹恶性疟原虫的基因组分析。
Nucleic Acids Res Suppl. 2002(2):223-4. doi: 10.1093/nass/2.1.223.
2
Genetic analysis of mefloquine-resistant mechanism of Plasmodium falciparum.恶性疟原虫耐甲氟喹机制的遗传分析
Nucleic Acids Symp Ser (Oxf). 2004(48):163-4. doi: 10.1093/nass/48.1.163.
3
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。
Am J Trop Med Hyg. 1994 Nov;51(5):648-58. doi: 10.4269/ajtmh.1994.51.648.
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Plasmodium falciparum: amplification and overexpression of pfmdr1 is not necessary for increased mefloquine resistance.恶性疟原虫:pfmdr1基因的扩增和过表达对于增加甲氟喹耐药性并非必要。
Exp Parasitol. 1996 Aug;83(3):295-303. doi: 10.1006/expr.1996.0077.
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Analysis of Pfmdr 1 gene in mefloquine-resistant Plasmodium falciparum.耐甲氟喹恶性疟原虫中Pfmdr 1基因的分析
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6
Selection for mefloquine resistance in Plasmodium falciparum is linked to amplification of the pfmdr1 gene and cross-resistance to halofantrine and quinine.恶性疟原虫对甲氟喹耐药性的选择与pfmdr1基因的扩增以及对卤泛群和奎宁的交叉耐药性有关。
Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):1143-7. doi: 10.1073/pnas.91.3.1143.
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pfmdr1 mutations contribute to quinine resistance and enhance mefloquine and artemisinin sensitivity in Plasmodium falciparum.pfmdr1突变导致恶性疟原虫对奎宁产生抗性,并增强其对甲氟喹和青蒿素的敏感性。
Mol Microbiol. 2005 Aug;57(4):913-26. doi: 10.1111/j.1365-2958.2005.04729.x.
8
Monitoring of in vitro susceptibilities and molecular markers of resistance of Plasmodium falciparum isolates from Thai-Myanmar border to chloroquine, quinine, mefloquine and artesunate.监测来自泰缅边境地区恶性疟原虫分离株对氯喹、奎宁、甲氟喹和青蒿琥酯的体外敏感性和耐药性分子标志物。
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9
Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number.恶性疟原虫对甲氟喹的耐药性及 pfmdr1 基因拷贝数增加。
Lancet. 2004;364(9432):438-447. doi: 10.1016/S0140-6736(04)16767-6.
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Role of pfmdr1 amplification and expression in induction of resistance to artemisinin derivatives in Plasmodium falciparum.疟原虫 falciparum 中 pfmdr1 扩增和表达在诱导对青蒿素衍生物耐药中的作用。
Antimicrob Agents Chemother. 2010 Jun;54(6):2455-64. doi: 10.1128/AAC.00947-09. Epub 2010 Mar 29.

引用本文的文献

1
Mefloquine exposure induces cell cycle delay and reveals stage-specific expression of the pfmdr1 gene.甲氟喹暴露诱导细胞周期延迟,并揭示 pfmdr1 基因的阶段特异性表达。
Antimicrob Agents Chemother. 2013 Feb;57(2):833-9. doi: 10.1128/AAC.01006-12. Epub 2012 Dec 3.
2
Molecular monitoring of Plasmodium falciparum drug susceptibility at the time of the introduction of artemisinin-based combination therapy in Yaoundé, Cameroon: implications for the future.在喀麦隆雅温得引入基于青蒿素的联合疗法时对恶性疟原虫药物敏感性的分子监测:对未来的影响。
Malar J. 2012 Apr 12;11:113. doi: 10.1186/1475-2875-11-113.
3
Plasmodium falciparum isolates with increased pfmdr1 copy number circulate in West Africa.
恶性疟原虫 Pfmdr1 拷贝数增加的分离株在西非流行。
Antimicrob Agents Chemother. 2010 Jul;54(7):3049-51. doi: 10.1128/AAC.00209-10. Epub 2010 Apr 19.