pH-Responsive Antimicrobial Peptide with Selective Killing Activity for Bacterial Abscess Therapy

The unusual acidic pH of the abscess milieu is an adverse factor that decreases the therapeutic efficacy of traditional antibiotics. Moreover, avoidingboth the undesired killing of commensal bacteria and the development of drug resistance remains difficult during abscess therapy. Hence, we synthesized a series of pH-responsive antimicrobial peptides equipped with efficient bacterial killingactivity at pH 6.5 and inactivity at pH 7.4. Among the peptides, F5 exhibitedoutstanding pH-responsive antimicrobial activity and low toxicity. Fluorescencespectroscopy and electron microscopy illustrated that F5 killed bacteria via amembrane-disruptive mechanism at acidic pH values. Mouse cutaneous abscessesrevealed that F5 was equipped with excellent therapeutic ability to reduce the bacterial load and cytokines without causing skin toxicity. In summary, this study reveals a strategy for selectively killing bacteria under the pathologic conditions of abscess sites while avoiding the elimination of commensal bacteria under normal physiological pH levels

Automated summary

This study synthesized a series of pH-responsive antimicrobial peptides, among which F5 exhibited outstanding pH-responsive activity and low toxicity. It killed bacteria through a membrane-disruptive mechanism at acidic pH values and showed excellent therapeutic ability in a mouse abscess model.