Antimalarial activity of cecropin antimicrobial peptides derived from Anopheles mosquitoes

• Published in: Antimicrobial agents and chemotherapy 2024-07, Vol.68 (7), p.e0031124
• Main Authors: Lou, Junchao, Zhang, Dongying, Wu, Jingyao, Zhu, Guoding, Zhang, Meihua, Tang, Jianxia, Fang, Yaqun, He, Xiaoqin, Cao, Jun
• Format: Article
• Language: English
• Subjects: Animals; Anopheles - drug effects; Anopheles - parasitology; Antimalarials - pharmacology; Antimicrobial Peptides - chemistry; Antimicrobial Peptides - pharmacology; Cecropins - pharmacology; Chloroquine - pharmacology; Drug Resistance - drug effects; Erythrocytes - drug effects; Erythrocytes - parasitology; Female; Humans; Insect Proteins - pharmacology; Malaria - drug therapy; Malaria - parasitology; Mechanisms of Action: Physiological Effects; Mice; Mosquito Vectors - drug effects; Mosquito Vectors - parasitology; Parasitic Sensitivity Tests; Parasitology; Plasmodium berghei - drug effects; Plasmodium falciparum - drug effects
• ISSN: 0066-4804; 1098-6596; 1098-6596
• DOI: 10.1128/aac.00311-24

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.