Nature2014-06-27 2:23 PM

对青蒿素有抗药性的疟疾的一个标记 A molecular marker of artemisinin-resistant Plasmodium falciparum malaria

论文摘要 

青蒿素抗药性在所分离出的东南亚疟疾病原体“镰刀形疟原虫”中的传播,可能会葬送为在全世界根除这种疾病所做努力。监测抗药性这一重要工作一直受阻于缺少一个分子标记。现在,Frédéric Ariey及同事识别出了“镰刀形疟原虫”青蒿素抗药性的一个主要决定因子,它也许能提供这样一个标记。他们发现,该寄生虫的PF3D7_1343700 kelch propeller domain (K-13 propeller)中发生的突变与抗药性最近的传播有关。与在2001和2012年间收集的样本所做比较显示,与抗药性的传播相一致的是,该标记的频率也增加了。除了提出一个有用的标记外,这些发现还有可能加深我们对抗药性怎样形成的认识,同时为在寻找新型抗疟疾药物中怎样绕过抗药性提供思路。

Abstract 

Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia threatens malaria control and elimination activities worldwide. To monitor the spread of artemisinin resistance, a molecular marker is urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7_1343700 kelch propeller domain (‘K13-propeller’) with artemisinin resistance in vitro and in vivo. Mutant K13-propeller alleles cluster in Cambodian provinces where resistance is prevalent, and the increasing frequency of a dominant mutant K13-propeller allele correlates with the recent spread of resistance in western Cambodia. Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance. K13-propeller polymorphism constitutes a useful molecular marker for large-scale surveillance efforts to contain artemisinin resistance in the Greater Mekong Subregion and prevent its global spread.

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