Cecropin D: A novel anti-Plasmodium peptide from the malaria vector Anopheles gambiae

Anophelinae malaria vector mosquitoes are exposed to a variety of microbes including Plasmodium. When infected, mosquitoes mount versatile immune responses, including the synthesis and release of antimicrobial peptides. Cecropins are one of the most widely distributed families of antimicrobial peptides in insects, with some non-mosquito members displaying anti-Plasmodium activity. Here we present a comprehensive investigation into the identification, molecular characterization, and functional implications of a novel cecropin member, Cecropin D (CecD), in the malaria vector Anopheles gambiae. We define member-specific amino acid signatures that will improve the systematic classification of the cecropin family. The CecD gene encodes a precursor peptide consisting of a signal sequence and a highly cationic mature peptide with antimicrobial properties. CecD is expressed at late larval stages with a significant upregulation upon immune challenge. We show that Cecropin D mediate immune defense to maintain larval viability. The synthetic Cecropin D peptide also exhibited potent activity against Plasmodium falciparum sporozoites, reducing their viability in a dose-dependent manner. Cecropin D represents a novel antimicrobial peptide relevant to malaria vectors, as it helps regulate the endogenous microbiota during mosquito development and holds promise as a potential agent to block malaria transmission.