I will investigate the hypothesis that antimicrobial peptides in insects deal with persistent infections and/or prevent the evolution of resistant bacterial mutants. This will be achieved by looking at two hitherto unrelated areas within a single conceptual and experimental framework: (a) how to prevent the evolution of bacterial resistance against antimicrobials? (b) Why is it adaptive for insects to exhibit long lasting costly immune responses?This research takes a novel approach to understand the evolution of drug resistance in pathogens, one of the most important applied evolutionary questions of our times. Insects produce potent antimicrobials that are considered as future novel antibiotic drugs and provide insight into a multidrug treatment shaped by natural selection. Elucidating the evolution of integrated immune responses will greatly enhance the understanding of immunity in insects, the most speciose metazoan taxon of great importance to human health (vectors) and nutrition (pollinators).I will use the beetle Tenebrio molitor to examine the temporal dynamics of an antibacterial response using proteomics. I will build on this using two series of experiments manipulating the antimicrobial response in-vivo, using RNAi gene knockdowns, and in in-vitro, using synthesised Tenebrio antimicrobials will be carried out. These experiments will investigate the response of the model pathogen Staphyloccocus aureus to the changes in the beetle s multidrug response. S. aureus resistance to these experimental selection arenas will be studied at the phenotypic and genomic level.The results from this research program will (a) inform antibiotic strategies in medical and veterinary science and (b) will change the way we understand the evolution of (insect) immunity