School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi, China.
Antimicrob Agents Chemother. 2024 Jul 9;68(7):e0031124. doi: 10.1128/aac.00311-24. Epub 2024 Jun 14.
The emergence of clinically drug-resistant malaria parasites requires the urgent development of new drugs. Mosquitoes are vectors of multiple pathogens and have developed resistance mechanisms against them, which often involve antimicrobial peptides (AMPs). An-cecB is an AMP of the malaria-transmitting mosquito genus , and we herein report its antimalarial activity against 3D7, the artemisinin-resistant strain 803, and the chloroquine-resistant strain Dd2 . We also demonstrate its anti-parasite activity , using the rodent malaria parasite (ANKA). We show that An-cecB displays potent antimalarial activity and that its mechanism of action may occur through direct killing of the parasite or through interaction with infected red blood cell membranes. Unfortunately, An-cecB was found to be cytotoxic to mammalian cells and had poor antimalarial activity . However, its truncated peptide An-cecB-1 retained most of its antimalarial activity and avoided its cytotoxicity . An-cecB-1 also showed better antimalarial activity . Mosquito-derived AMPs may provide new ideas for the development of antimalarial drugs against drug-resistant parasites, and An-cecB has potential use as a template for antimalarial peptides.
临床上耐药疟原虫的出现需要迫切开发新的药物。蚊子是多种病原体的载体,已经发展出针对这些病原体的耐药机制,其中常常涉及抗菌肽 (AMPs)。An-cecB 是传播疟疾的蚊子属的一种 AMP,我们在此报告其对 3D7(青蒿素耐药株)、803(氯喹耐药株)和 Dd2(氯喹耐药株)的抗疟活性。我们还使用啮齿动物疟原虫 (ANKA)证明了其抗寄生虫活性。我们表明 An-cecB 具有很强的抗疟活性,其作用机制可能通过直接杀死寄生虫或通过与感染的红细胞膜相互作用来实现。不幸的是,An-cecB 被发现对哺乳动物细胞具有细胞毒性,并且对疟原虫的活性较差。然而,其截断肽 An-cecB-1 保留了大部分抗疟活性并避免了其细胞毒性。An-cecB-1 也显示出更好的抗疟活性。蚊子来源的 AMP 可能为开发针对耐药寄生虫的抗疟药物提供新的思路,并且 An-cecB 有可能作为抗疟肽的模板使用。