Atovaquone Tolerance in Plasmodium falciparum Parasites Selected for High-Level Resistance to a Dihydroorotate Dehydrogenase Inhibitor
Atovaquone Tolerance in Plasmodium falciparum Parasites Selected for High-Level Resistance to a Dihydroorotate Dehydrogenase Inhibitor
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DOI：
10.1128/aac.02347-14
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发表时间：
2015-01-01
影响因子：
4.9
通讯作者：
Rathod, Pradipsinh K.
中科院分区：
文献类型：
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作者：
Guler, Jennifer L.;White, John, III;Rathod, Pradipsinh K.
阿托伐醌是马拉酮的一种成分，马拉酮是一种广泛处方的抗疟复方制剂，针对疟疾呼吸。在这里，我们表明，寄生虫具有高水平的耐药二氢乳清酸脱氢酶抑制剂表现出意想不到的阿托伐醌耐受性。幸运的是，使用马来酰亚胺的第二个伙伴氯胍可以减少耐受性。重要的是要了解呼吸和嘧啶生物合成之间的“遗传串扰”，因为许多抗疟药物开发计划针对这两个看似独立的途径。
Atovaquone is a component of Malarone, a widely prescribed antimalarial combination, that targets malaria respiration. Here we show that parasites with high-level resistance to an inhibitor of dihydroorotate dehydrogenase demonstrate unexpected atovaquone tolerance. Fortunately, the tolerance is diminished with proguanil, the second partner in Malarone. It is important to understand such "genetic cross talk" between respiration and pyrimidine biosynthesis since many antimalarial drug development programs target these two seemingly independent pathways.