In vitro characterization of a novel designer peptide to treat systemic infections caused by Gram-negative human pathogens

The incidence of serious bacterial and fungal infections is increasing despite remarkable advances in antibiotic therapy. At a time of the rapid emergence of drug-resistant bacterial strains, there is an urgent need to develop new antimicrobial compounds with novel modes of action. Antimicrobial peptides (AMPs) of the innate immune system appear very promising. Starting from the 2 kDa Oncopeltus antibacterial peptide 4, which was originally isolated from milkweed bug (Oncopeltus fasciatus), we optimized the antibacterial activities against Gram-negative pathogens. The current focus is on three species of Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae) and two non-fermenting species (Acinetobacter baumannii and Pseudomonas aeruginosa). These are clinically relevant species, causing serious health care problems due to the acquisition of multiple resistance traits. The optimized peptide leads (called oncocin) showed minimal inhibitory concentrations (MIC) between 0.25 and 4 μg/mL against a panel of 32 different strains and clinical isolates.