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

Area of Science:

• Biochemistry
• Microbiology
• Drug Discovery

Background:

• Abscesses create an acidic environment (pH 6.5) that reduces antibiotic effectiveness.
• Current therapies struggle to eliminate pathogens without harming beneficial bacteria or causing resistance.

Purpose of the Study:

• To develop novel pH-responsive antimicrobial peptides (AMPs) for targeted abscess treatment.
• To evaluate the efficacy and safety of these AMPs in vitro and in vivo.

Main Methods:

• Synthesis of pH-responsive AMPs.
• Antimicrobial activity testing at different pH levels (6.5 vs. 7.4).
• Mechanism of action studies using fluorescence spectroscopy and electron microscopy.
• In vivo efficacy evaluation in a mouse cutaneous abscess model.

Main Results:

• The peptide F5 demonstrated potent antimicrobial activity at pH 6.5 and negligible activity at pH 7.4.
• F5 exhibited low toxicity and killed bacteria via membrane disruption at acidic pH.
• In vivo studies showed F5 effectively reduced bacterial load and cytokines in abscesses without skin toxicity.

Conclusions:

• pH-responsive AMPs, like F5, offer a promising strategy for selective bacterial eradication in acidic abscess environments.
• This approach minimizes collateral damage to commensal microbiota and reduces the risk of antimicrobial resistance.