This technology is a panel of derivatives of the wasp-derived AMP polybia-CP. While wild type polybia-CP is a potent antimicrobial, it is also highly toxic to human cells. These inventors rationally designed changes that stabilize the helical structures and tune physicochemical properties of the polybia-CP parent compound, which respectively resulted in increased antibiotic activity against bacteria and decreased toxicity in human cells. The two lead compound derivatives are highly effective in treating P. aeruginosa infections in an in vivo mouse model. A single dose of the top polybia-CP derivative is five orders of magnitude more effective than the parent compound and was able to nearly eradicate P. aeruginosa in the skin of infected mice within 4 days.