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一个分子标志物的阿尔特米西宁耐药的Plasmodium falciparum疟疾

Frédéric Ariey¹, Benoit Witkowski², Chanaki Amaratunga³

¹1] Institut Pasteur, Parasite Molecular Immunology Unit, 75724 Paris Cedex 15, France [2] Centre National de la Recherche Scientifique, Unité de Recherche Associée 2581, 75724 Paris Cedex 15, France [3] Institut Pasteur, Genetics and Genomics of Insect Vectors Unit, 75724 Paris Cedex 15, France (F.A.); Institut Pasteur, Functional Genetics of Infectious Diseases Unit, 75724 Paris Cedex 15, France (J.B.); Centre de Physiopathologie de Toulouse-Purpan, Institut National de la Santé et de la Recherche Médicale UMR1043, Centre National de la Recherche Scientifique UMR5282, Université Toulouse III, 31024 Toulouse Cedex 3, France Institut Pasteur, Unité de Biologie et Génétique du Paludisme, Team Malaria Targets and Drug Development, 75724 Paris Cedex 15, France (J.-C.B.).

|December 20, 2013

概括

疟疾在Plasmodium falciparum中的阿尔特米西宁耐药性是一个全球性的威胁. K13螺旋基因的突变被确定为跟踪和控制素耐药性的关键分子标记物,特别是在东南亚.

科学领域:

遗传学是一个遗传学.
寄生虫学的寄生虫学
分子生物学分子生物学

背景情况:

疟原虫 (疟原虫) 对素衍生物的耐药性对全球疟疾控制工作,尤其是东南亚地区,是一个重大挑战.
抗素耐药性的传播威胁着全球的疟疾消除目标.
一个可靠的分子标志物对于监测素抗性的地理传播至关重要.

研究的目的:

为了识别与Plasmodium falciparum中艺术素抵抗相关的分子标记物.
调查K13螺旋领域突变在素抗性的作用.
评估K13-螺旋突变作为对素耐药性的监测工具的有用性.

主要方法:

来自非洲和柬埔寨的临床分离物体的抗美西宁的Plasmodium falciparum寄生虫系的全基因组测序.
在PF3D7_1343700螺旋域 (K13-螺旋) 中突变的关联分析与体外和体内素耐药性表型.
在柬埔寨突变K13螺旋等位基因频率的地理映射.

主要成果:

在K13-螺旋领域的突变与体外和体内素耐药性强烈相关.
发现突变的K13螺旋等位基因在柬埔寨省份聚集在一起,在柬埔寨省份有普遍的素抗性.
主导突变K13螺旋等位基因的频率增加与柬埔寨西部抗药性传播相关.

结论:

K13-螺旋突变是Plasmodium falciparum中素耐药性的关键决定因素.
K13螺旋多态性作为一种有价值的分子标记物,用于大规模监测素耐药性.
通过K13螺旋监测,有效地制大公河次区域的素耐药性,并防止全球传播.

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