Trp-containing Peptides with Therapeutic Potential for Cutibacterium acnes Infection

Area of Science:

• Dermatology and Microbiology
• Peptide Therapeutics
• Natural Product Chemistry

Background:

• Acne vulgaris is a common skin condition driven by Cutibacterium acnes (C. acnes) bacteria.
• C. acnes contributes to skin inflammation and pustule formation.
• Current treatments face challenges with resistance and side effects.

Purpose of the Study:

• To develop and synthesize novel antimicrobial peptides (AMPs) from Rana chensinensis skin secretions.
• To evaluate the efficacy of these AMPs against C. acnes.
• To investigate the mechanism of action and therapeutic potential for acne vulgaris.

Main Methods:

• Synthesis and screening of Trp-containing antimicrobial peptides (AMPs).
• Minimum Inhibitory Concentration (MIC) assays for antibacterial activity.
• Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM) for morphological changes.
• Zeta potential, Disc3(5), and Live/Dead assays to assess membrane disruption.
• Biofilm inhibition assays.
• In vivo testing in acne mouse models.

Main Results:

• Trp-containing AMPs exhibited potent antibacterial activity against C. acnes.
• Microscopy revealed cell surface damage and membrane disruption, leading to cell death.
• AMPs caused leakage of intracellular contents (nucleic acid, K+, Ca2+).
• Biofilm formation and mature biofilms were suppressed.
• The peptide I4WL5W showed dual antibacterial and anti-inflammatory effects in vivo, reducing bacterial load and inflammatory cytokines (TNF-α, IL-6, IL-1β).

Conclusions:

• Trp-containing AMPs derived from frog skin secretions are effective against C. acnes.
• These AMPs act by disrupting bacterial cell membranes.
• The peptide I4WL5W demonstrates significant potential as a dual-action therapeutic for acne vulgaris, with low cytotoxicity.