Novel non-cytotoxic antimicrobial peptides WSKK11 and WSRR11 with potent activity against Cutibacterium acnes

J Antimicrob Chemother. 2022 Mar 31;77(4):1012-1019. doi: 10.1093/jac/dkac014.

Abstract

Objectives: Cutibacterium acnes is one of the common multifactorial causes that play an important role in the pathophysiology of acne vulgaris. We aimed to develop novel antimicrobial peptides for reduction of the hypercolonization.

Methods: Six cationic peptides were derived by de novo designation. The antimicrobial and cytotoxic activities of peptides were investigated. The peptide conformation was determined by circular dichroism spectrometry. The antimicrobial effects of peptides were evaluated using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and DNA-binding ability assay.

Results: Among designed peptides, WSKK11 and WSRR11 were effective antimicrobials against C. acnes at MICs of 128 and 64 mg/L, respectively. The MICs of WSKK11 against Staphylococcus epidermidis, Staphylococcus aureus and Candida albicans were 8, 8 and 32 mg/L, while those of WSRR11 were 64, 32 and 32 mg/L, respectively. WSKK11 and WSRR11 were less toxic to human erythrocytes (<2%) and not toxic to macrophages, keratinocytes and fibroblasts up to 512 mg/L. WSKK11 and WSRR11 mostly revealed the conformation of the undefined or random coil structures under mimicked environmental conditions. The peptides affected cell surfaces and cell membranes of C. acnes as well as possibly translocating through the cell membrane, observed by a combination of SEM and TEM, respectively. WSKK11 and WSRR11 had the ability to bind bacterial DNA.

Conclusions: The two novel antimicrobial peptides WSKK11 and WSRR11 are members of a new class of antimicrobial agents that could deal with acne problems. Therefore, the antimicrobial peptides may be promising novel active agents for dermatological, beauty and cosmeceutical applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acne Vulgaris* / drug therapy
  • Anti-Bacterial Agents / pharmacology
  • Antimicrobial Peptides*
  • Humans
  • Microbial Sensitivity Tests
  • Propionibacterium acnes / physiology

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Peptides

Grants and funding