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<p>The antimicrobial effect of antimicrobial peptides is typically slow; they can be rapidly biodegraded and often have non-selective toxicity and elaborate sequences. Here we report a short peptide that is activated by ultrasound, that shows high broad-spectrum antibacterial efficiency (&gt;99%) against clinically isolated methicillin-resistant bacteria (specifically, <i>Staphylococcus aureus</i>, <i>Escherichia coli</i>, <i>Staphylococcus epidermidis</i>, <i>Enterobacter cancerogenus</i> and <i>Pseudomonas aeruginosa</i>) with 15 min of ultrasound irradiation, and that has negligible toxicity and low self-antibacterial activity. We selected the peptide, FFRKSKEK (a segment from the human host-defence LL-37 peptide), from a library of peptides with piezoelectric diphenylalanine (FF) sequences, low toxicity, hydrophobicity and net positive charge. We show via all-atom molecular dynamics simulations that ultrasound amplifies the membrane-penetrating ability of peptides with FF sequences and that its piezoelectric polarization generates reactive-oxygen species and disturbs bacterial electron-transport chains. In a goat model of hard-to-treat intervertebral infection, the sonosensitive peptide led to better outcomes than vancomycin. Antimicrobial peptides activated by ultrasound may offer a clinically relevant strategy for combating antibiotic-resistant infections.</p>

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A sonosensitive diphenylalanine-based broad-spectrum antimicrobial peptide

  • 期刊论文

  • 发表日期：

    2025年5月2日

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  • Xiaoguang Zhang,
  • Xiaobo Feng,
  • Liang Ma,
  • Jie Lei,
  • Gaocai Li,
  • Weifeng Zhang,
  • Huaizhen Liang,
  • Bide Tong,
  • Di Wu,
  • Cao Yang,
  • Lei Tan

摘要

The antimicrobial effect of antimicrobial peptides is typically slow; they can be rapidly biodegraded and often have non-selective toxicity and elaborate sequences. Here we report a short peptide that is activated by ultrasound, that shows high broad-spectrum antibacterial efficiency (>99%) against clinically isolated methicillin-resistant bacteria (specifically, Staphylococcus aureus, Escherichia coli, Staphylococcus epidermidis, Enterobacter cancerogenus and Pseudomonas aeruginosa) with 15 min of ultrasound irradiation, and that has negligible toxicity and low self-antibacterial activity. We selected the peptide, FFRKSKEK (a segment from the human host-defence LL-37 peptide), from a library of peptides with piezoelectric diphenylalanine (FF) sequences, low toxicity, hydrophobicity and net positive charge. We show via all-atom molecular dynamics simulations that ultrasound amplifies the membrane-penetrating ability of peptides with FF sequences and that its piezoelectric polarization generates reactive-oxygen species and disturbs bacterial electron-transport chains. In a goat model of hard-to-treat intervertebral infection, the sonosensitive peptide led to better outcomes than vancomycin. Antimicrobial peptides activated by ultrasound may offer a clinically relevant strategy for combating antibiotic-resistant infections.