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.
Keywords: abdominal infection; antimicrobial peptide; broad-spectrum antimicrobials; charge/hydrophobicity balance; sequence optimization.
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