氯喹耐药的疟原虫中一种新的自噬相关机制。
An Alternative Autophagy-Related Mechanism of Chloroquine Drug Resistance in the Malaria Parasite.
机构信息
Aly Lab, Beykoz Institute of Life Sciences and Biotechnology, Bezmialem Vakif University, Istanbul, Turkey.
Department of Biotechnology, Institute of Health Sciences, Bezmialem Vakif University, Istanbul, Turkey.
出版信息
Antimicrob Agents Chemother. 2022 Dec 20;66(12):e0026922. doi: 10.1128/aac.00269-22. Epub 2022 Nov 7.
Abstract
We generated highly chloroquine (CQ)-resistant (ResCQ) Plasmodium yoelii parasites by stepwise exposure to increasing concentrations of CQ and CQ-sensitive parasites (SenCQ) by parallel mock treatments. No mutations in genes that are associated with drug resistance were detected in ResCQ clones. Autophagy-related genes were highly upregulated in SenCQ compared to ResCQ parasites during CQ treatment. This indicates that CQ resistance can be developed in the malaria parasite by the inhibition of autophagy as an alternative drug resistance mechanism.
摘要
我们通过逐步暴露于逐渐增加的氯喹 (CQ) 浓度以及平行的模拟处理来生成高度耐氯喹 (ResCQ) 的约氏疟原虫寄生虫，而在 ResCQ 克隆中未检测到与耐药性相关的基因突变。在 CQ 处理期间，与 SenCQ 寄生虫相比，自噬相关基因在 ResCQ 寄生虫中高度上调。这表明在疟原虫中，自噬的抑制可以作为一种替代耐药机制来开发抗氯喹耐药性。
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