Plasmodium falciparum Artemisinin Resistance: The Effect of Heme, Protein Damage, and Parasite Cell Stress Response.,ACS Infectious Diseases

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Plasmodium falciparum Artemisinin Resistance: The Effect of Heme, Protein Damage, and Parasite Cell Stress Response.
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2020-04-23 , DOI: 10.1021/acsinfecdis.9b00527
Melissa R Rosenthal ₁ , Caroline L Ng ₁

Affiliation

Despite a significant decline in morbidity and mortality over the last two decades, in 2018 there were 228 million reported cases of malaria and 405000 malaria-related deaths. Artemisinin, the cornerstone of artemisinin-based combination therapies, is the most potent drug in the antimalarial armamentarium against falciparum malaria. Heme-mediated activation of artemisinin and its derivatives results in widespread parasite protein alkylation, which is thought to lead to parasite death. Alarmingly, cases of decreased artemisinin efficacy have been widely detected across Cambodia and in neighboring countries, and a few cases have been reported in the Guiana Shield, India, and Africa. The grim prospect of widespread artemisinin resistance propelled a concerted effort to understand the mechanisms of artemisinin action and resistance. The identification of genetic markers and the knowledge of molecular mechanisms underpinning artemisinin resistance allow prospective surveillance and inform future drug development strategies, respectively. Here, we highlight recent advances in our understanding of how parasite vesicle trafficking, hemoglobin digestion, and cell stress responses contribute to artemisinin resistance.

中文翻译：

恶性疟原虫青蒿素抗性：血红素、蛋白质损伤和寄生虫细胞应激反应的影响。

尽管过去 20 年发病率和死亡率显着下降，但 2018 年报告的疟疾病例为 2.28 亿，与疟疾相关的死亡人数为 40.5 万。青蒿素是基于青蒿素的联合疗法的基石，是对抗恶性疟原虫的抗疟药物中最有效的药物疟疾。血红素介导的青蒿素及其衍生物的激活导致广泛的寄生虫蛋白质烷基化，这被认为会导致寄生虫死亡。令人担忧的是，在柬埔寨和邻国广泛发现了青蒿素药效降低的病例，在圭亚那地盾、印度和非洲也报告了一些病例。普遍存在的青蒿素耐药性的严峻前景促使人们齐心协力了解青蒿素的作用和耐药机制。遗传标记的鉴定和支持青蒿素耐药性的分子机制的知识分别允许进行前瞻性监测并为未来的药物开发策略提供信息。在这里，我们重点介绍了我们对寄生虫囊泡运输、血红蛋白消化、

更新日期：2020-04-23

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