Mosquito Antimicrobial Peptides: Molecular Diversity, Mechanisms of Action, and Translational Potential

Mosquito antimicrobial peptides (AMPs) contribute to innate defense against bacteria, fungi, parasites, and, in some experimental contexts, arboviruses. This narrative review evaluates endogenous mosquito AMP families across Aedes, Anopheles, and Culex species and clearly separates them from heterologous peptides introduced into mosquitoes for transmission-blocking studies. The best-supported endogenous families are cecropins, defensins, gambicin, attacin, and diptericin, although gene repertoires vary among mosquito lineages. Mechanistic evidence is strongest for membrane interaction by individual cecropins and defensins. Evidence for intracellular or redox mechanisms is more limited and peptide- and assay-specific; for example, mitochondrial effects have been demonstrated for Anopheles albimanus cecropin 3 in isolated rat cardiac mitochondria, whereas DNA binding and membrane permeabilization have been shown for an Aedes aegypti cecropin A derivative in Pseudomonas aeruginosa. Scorpine, magainin, and human defensin 5 are not mosquito AMPs and are considered separately as heterologous antiplasmodial effectors. Toll and immune deficiency (IMD) pathways regulate mosquito immune genes through NF-κB-family transcription factors, whereas Janus kinase-signal transducer and activator of transcription (JAK-STAT) is a distinct cytokine-signaling pathway. Translational approaches-including transgenic expression, paratransgenesis, Wolbachia-based control, and peptide engineering-remain promising but require cautious interpretation because efficacy, mechanism, ecological safety, horizontal gene transfer, regulatory oversight, and durability have not been resolved uniformly. By distinguishing direct peptide activity from genetic, expression-only, and inferential evidence, this review provides a more rigorous framework for evaluating mosquito AMPs and their potential use in vector-borne disease control.