A safe and multitask antimicrobial decapeptide: the road from de novo design to the structural and functional characterization

Antimicrobial peptides (AMPs) are excellent candidates to fight multi-resistant pathogensworldwide and are considered promising bio-preservatives to control microbial spoilage throughfood processing. To date, designing de novo AMPs with high therapeutic indexes, low-cost synthesis,high resistance, and bioavailability, remains a challenge. In this study, a novel decapeptide,named RiLK1, was rationally designed starting from the sequence of the previously characterizedAMP 1018-K6, with the aim of developing short peptides, and promoting higher selectivityover mammalian cells, antibacterial activity, and structural resistance under dierent salt, pH,and temperature conditions. Interestingly, RiLK1 displayed a broad-spectrum of bactericidal activityagainst Gram-positive and Gram-negative bacteria, including multidrug resistant clinical isolatesof Salmonella species, with Minimal Bactericidal Concentration (MBC) values in low micromolarrange, and it was eective even against two fungal pathogens with no evidence of cytotoxicity onhuman keratinocytes and fibroblasts. Moreover, RiLK1-activated polypropylene films were revealedto eciently prevent the growth of microbial spoilage, possibly improving the shelf life of fresh foodproducts. These results suggested that de novo designed peptide RiLK1 could be the first candidatefor the development of a promising class of decameric and multitask antimicrobial agents to overcomedrug-resistance phenomena.