Mechanisms of artemisinin resistance in the rodent malaria pathogen Plasmodium yoelii
Mechanisms of artemisinin resistance in the rodent malaria pathogen Plasmodium yoelii
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DOI：
10.1128/aac.44.2.344-347.2000
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发表时间：
2000-02-01
影响因子：
4.9
通讯作者：
Meshnick, SR
中科院分区：
文献类型：
--
作者：
Walker, DJ;Pitsch, JL;Meshnick, SR
青蒿素及其衍生物是目前在东南亚广泛使用的重要新型抗疟药物。临床相关的青蒿素耐药尚未报道，但很可能会发生。为了了解疟疾寄生虫如何对这种药物产生耐药性，我们研究了小鼠疟疾寄生虫约氏疟原虫对青蒿素的耐药性。青蒿素耐药菌株（ART）对青蒿素的敏感性约为敏感菌株NS的四分之一，其体外积累的放射性标记药物量减少43% （P < 0.01）。在寄生虫体内，药物在两种菌株中似乎与相同的寄生虫蛋白发生反应。翻译控制的肿瘤蛋白（青蒿素靶蛋白之一）在菌株之间没有差异。DNA序列无差异，但耐药菌株的蛋白表达量是敏感菌株的2.5倍（P < 0.01）。因此，青蒿素耐药的表型似乎是多因素的。
Artemisinin and its derivatives are important new antimalarials which are now used widely in Southeast Asia. Clinically relevant artemisinin resistance has not yet been reported but is likely to occur, In order to understand how the malaria parasite might become resistant to this drug, we studied artemisinin resistance in the murine malaria parasite Plasmodium yoelii. The artemisinin-resistant strain (ART), which is approximately fourfold less sensitive to artemisinin than the sensitive NS strain, accumulated 43% less radiolabeled drug in vitro (P < 0.01),Within the parasite, the drug appeared to react with the same parasite proteins in both strains. The translationally controlled tumor protein, one of the artemisinin target proteins, did not differ between the strains. No DNA sequence difference was found, but the resistant strain was found to express 2.5-fold-more protein than the sensitive strain (P < 0.01). Thus, the phenotype of artemisinin resistance in P, yoelii appears to be multifactorial.