A molecular marker of artemisinin-resistant Plasmodium falciparum malaria.
A molecular marker of artemisinin-resistant Plasmodium falciparum malaria.
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作者：
东南亚恶性疟原虫对青蒿素衍生物的抗药性威胁着全世界的疟疾控制和消除活动。为了监测青蒿素耐药性的传播，迫切需要一种分子标记。在这里，使用来自非洲的青蒿素抗性寄生虫系和来自柬埔寨的临床寄生虫分离株的全基因组测序，我们将PF3D7_1343700 kelch螺旋桨结构域（“K13-螺旋桨”）中的突变与体外和体内的青蒿素抗性相关联。突变的K13-螺旋桨等位基因聚集在柬埔寨省的阻力是普遍的，和显性突变的K13-螺旋桨等位基因的频率增加与最近在柬埔寨西部蔓延的阻力。突变等位基因的存在、体外寄生虫存活率和体内寄生虫清除率之间的强相关性表明，K13-螺旋桨突变是青蒿素耐药性的重要决定因素。K13-螺旋桨多态性是一个有用的分子标记，用于大规模监测工作，以遏制大湄公河次区域的青蒿素耐药性，并防止其全球传播。
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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影响因子：
16
作者：
Lobo, CA;Fujioka, H;Kumar, N
通讯作者：
Kumar, N
影响因子：
10.5
作者：
Itoh, K;Wakabayashi, N;Yamamoto, M
通讯作者：
Yamamoto, M
DOI：
10.1073/pnas.1104063108
发表时间：
2011-07-12
影响因子：
11.1
作者：
Klonis, Nectarios;Crespo-Ortiz, Maria P.;Tilley, Leann
通讯作者：
Tilley, Leann
影响因子：
3
作者：
Bozdech, Z;Ginsburg, H
通讯作者：
Ginsburg, H
影响因子：
4.8
作者：
Bhisutthibhan, J;Pan, XQ;Meshnick, SR
通讯作者：
Meshnick, SR