Optimized Charge/Hydrophobicity Balance of Antimicrobial Peptides Against Polymicrobial Abdominal Infections

Antimicrobial peptides (AMPs) potentially serve as ideal antimicrobial agents for the treatment of polymicrobial abdominal infections due to their broad-spectrum antimicrobial activity and excellent biocompatibility. However, the balance of chain length, positive charges, and hydrophobicity on the antimicrobial activity of AMPs are still far from being optimal. Herein, a series of AMPs ([KX]_n-NH₂, X = Ile, Leu or Phe, n = 3, 4, 5, or 6) with varied charges and hydrophobicity for the treatment of polymicrobial abdominal infections are designed. Specifically, [KI]₄-NH₂ peptide exhibits the best in vitro antimicrobial activity against Gram-positive and -negative bacteria, as well as fungal strains. Based on the good cell biocompatibility, [KI]₄-NH₂ peptide is found to have negligible in vivo toxicity at the dosage of up to 28 mg kg^-1. Furthermore, great in vivo therapeutic efficacy of [KI]₄-NH₂ peptide against S. typhimurium is demonstrated in the mice abdominal infection model. The design of short sequence of antimicrobial peptides with a charge/hydrophobicity balanced structures provides a simple and efficient strategy for potential clinical applications of antimicrobial peptide-based biomaterials in a variety of bacterial infection diseases.