Malaria remains a significant global public health challenge. The widespread prevalence of malaria, the limitations of current control measures, and the urgent demand for novel chemoprophylactic and chemotherapeutic agents drive the exploration of alternative treatment strategies. Antimicrobial peptides (AMPs) have emerged as promising candidates to target malaria parasites, owing to their diverse mechanisms of action and immunomodulatory properties. Additionally, AMPs offer potential as transmission-blocking agents by targeting parasites within mosquito vectors. Upon Plasmodium infection, mosquitoes recruit a repertoire of endogenous effectors, including various AMP families, to counteract parasite development. However, knowledge of AMP diversity and function in the primary malaria vector Anopheles gambiae remains limited. To address this gap, we conducted a comprehensive in silico survey to identify novel mosquito AMPs. Through data mining of publicly available An. gambiae genomic resources, we uncovered over 30 candidate AMP-encoding genes, encompassing at least eight distinct multigenic families. Gene expression profiling via qPCR assessed their spatial-temporal distribution across mosquito tissues and developmental stages, as well as their responses to bacterial challenges and Plasmodium falciparum infection. Furthermore, 12 peptides were selected for in vitro antimicrobial activity assays against a panel of bacteria, fungi and Plasmodium and their mode of action on bacterial surface was investigated. Comparative genomic analyses also identified orthologous AMP genes in several additional mosquito species. This study significantly expands the known repertoire of mosquito AMPs, providing valuable insights into vector immunity and laying the groundwork for the development of novel vector-targeted malaria control strategies.
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