Linearized esculentin-2EM shows pH dependent antibacterial activity with an alkaline optimum

Area of Science:

• Antimicrobial Peptides
• Biophysics
• Molecular Biology

Background:

• Antimicrobial peptides (AMPs) are crucial in innate immunity.
• Esculentin 2EM (E2EM) is a peptide with known antimicrobial properties.
• The pH-dependent activity of E2EM-lin remains largely unexplored.

Purpose of the Study:

• To investigate the pH-dependent activity of linearized esculentin 2EM (E2EM-lin).
• To elucidate the mechanism of E2EM-lin's membranolytic action.
• To explore the potential applications of E2EM-lin.

Main Methods:

• Bacterial lysis assays against Gram-positive and Gram-negative bacteria.
• Circular dichroism spectroscopy to determine α-helical structure.
• Membrane penetration and lysis force measurements.
• Theoretical analysis of peptide-membrane interactions.

Main Results:

• E2EM-lin exhibited potent activity against Gram-positive bacteria (MLCs ≤ 6.25 μM) and weak activity against Gram-negative bacteria (MLCs ≥ 75.0 μM).
• Peptide α-helical structure, membrane penetration, and lysis increased with pH from 6 to 8.
• A novel pore-forming model involving a tilted, α-helical structure was proposed, with alkaline pH optima.

Conclusions:

• E2EM-lin demonstrates pH-dependent antimicrobial activity, enhanced under alkaline conditions.
• The peptide's mechanism involves forming tilted, α-helical structures that lyse bacterial membranes.
• E2EM-lin shows potential for therapeutic applications, such as wound disinfection and food preservation.