Cecropins contribute toDrosophilahost defence against fungal and Gram-negative bacterial infection

ABSTRACTCecropins are small helical secreted peptides with antimicrobial activity that are widely distributed among insects. Genes encoding Cecropins are strongly induced upon infection, pointing to their role in host-defence. InDrosophila, fourCecropingenes clustered in the genome (CecA1, CecA2, CecBandCecC) are expressed upon infection downstream of the Toll and Imd pathways. In this study, we generated a short deletionΔCecA-Cremoving the wholeCecropinlocus. Using theΔCecA-Cdeficiency alone or in combination with other antimicrobial peptide (AMP) mutations, we addressed the function of Cecropins in the systemic immune response.ΔCecA-Cflies were viable and resisted challenge with various microbes as wild-type. However, removingΔCecA-Cin flies already lacking ten other AMP genes revealed a role for Cecropins in defence against Gram-negative bacteria and fungi. Measurements of pathogen loads confirm that Cecropins contribute to the control of certain Gram-negative bacteria, notablyEnterobacter cloacaeandProvidencia heimbachae. Collectively, our work provides the first genetic demonstration of a role for Cecropins in insect host defence, and confirms theirin vivoactivity primarily against Gram-negative bacteria and fungi. Generation of a fly line (ΔAMP14) that lacks fourteen immune inducible AMPs provides a powerful tool to address the function of these immune effectors in host-pathogen interactions and beyond.