PDF(Pubmed)
Abstract：
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 Anopheles, and we herein report its antimalarial activity against Plasmodium falciparum 3D7, the artemisinin-resistant strain 803, and the chloroquine-resistant strain Dd2 in vitro. We also demonstrate its anti-parasite activity in vivo, using the rodent malaria parasite Plasmodium berghei (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 in vivo. However, its truncated peptide An-cecB-1 retained most of its antimalarial activity and avoided its cytotoxicity in vitro. An-cecB-1 also showed better antimalarial activity in vivo. 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.
摘要：
临床上耐药的疟疾寄生虫的出现迫切需要开发新药物。蚊子是多种病原体的传播媒介，已经形成了对它们的抗性机制，通常涉及抗菌肽（AMP）。An-cecB是疟疾传播蚊子按蚊的AMP，我们在此报告了其体外对恶性疟原虫3D7，青蒿素抗性菌株803和氯喹抗性菌株Dd2的抗疟活性。我们还证明了它在体内的抗寄生虫活性，使用啮齿动物疟疾寄生虫伯氏疟原虫（ANKA）。我们表明，An-cecB具有有效的抗疟活性，其作用机制可能是通过直接杀死寄生虫或通过与感染的红细胞膜相互作用而发生的。不幸的是,发现An-cecB对哺乳动物细胞具有细胞毒性，并且在体内具有较差的抗疟活性。然而,其截短的肽An-cecB-1保留了其大部分抗疟疾活性，并避免了其在体外的细胞毒性。An-cecB-1在体内也显示出更好的抗疟活性。蚊源AMPs可能为开发抗耐药寄生虫的抗疟药物提供新思路,和An-cecB具有作为抗疟疾肽的模板的潜在用途。
