Optimized Charge/Hydrophobicity Balance of Antimicrobial Peptides Against Polymicrobial Abdominal Infections
Macromolecular bioscience(2023)
摘要
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. A charge/hydrophobicity balanced antimicrobial peptide ([KI]4-NH2) is optimized for the treatment of polymicrobial abdominal infections. [KI]4-NH2 not only has a simple and short sequence to minimize the high production cost, but also has good broad-spectrum antimicrobial activity and biosafety against bacteria and fungi in vivo and in vitro.image
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关键词
abdominal infection,antimicrobial peptide,broad-spectrum antimicrobials,charge/hydrophobicity balance,sequence optimization
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