Plasmodium falciparum and Plasmodium vivax, the two protozoan parasite species that cause the majority of cases of human malaria, have developed resistance to nearly all known antimalarials. The ability of malaria parasites to develop resistance is primarily due to the high numbers of parasites in the infected person's bloodstream during the asexual blood stage of infection in conjunction with the mutability of their genomes. Identifying the genetic mutations that mediate antimalarial resistance has deepened our understanding of how the parasites evade our treatments and reveals molecular markers that can be used to track the emergence of resistance in clinical samples. In this review, we examine known genetic mutations that lead to resistance to the major classes of antimalarial medications: the 4-aminoquinolines (chloroquine, amodiaquine and piperaquine), antifolate drugs, aryl amino-alcohols (quinine, lumefantrine and mefloquine), artemisinin compounds, antibiotics (clindamycin and doxycycline) and a napthoquinone (atovaquone). We discuss how the evolution of antimalarial resistance informs strategies to design the next generation of antimalarial therapies.

中文翻译：

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抗疟药物耐药性的基因组结构。


恶性疟原虫和间日疟原虫是导致大多数人类疟疾病例的两种原生动物寄生虫，它们已经对几乎所有已知的抗疟药产生了耐药性。疟疾寄生虫产生抗药性的能力主要是由于在感染的无性血液阶段，感染者的血液中存在大量寄生虫及其基因组的可变性。识别介导抗疟耐药性的基因突变加深了我们对寄生虫如何逃避治疗的理解，并揭示了可用于追踪临床样本中耐药性出现的分子标记。在这篇综述中，我们检查了导致对主要类别抗疟药物产生耐药性的已知基因突变：4-氨基喹啉（氯喹、阿莫地喹和哌喹）、抗叶酸药物、芳基氨基醇（奎宁、本芴醇和甲氟喹）、青蒿素化合物、抗生素（克林霉素和强力霉素）和萘醌（阿托伐醌）。我们讨论抗疟疾耐药性的进化如何为设计下一代抗疟疾疗法的策略提供信息。