Therapeutic potential, antimicrobial activity against acne-causing bacteria, and modes of action of WKK10 and WRR10, novel cationic antimicrobial peptides

Abstract

Although antimicrobial peptides possess potent antimicrobial activities, the high cost of production, based on amino acid length, has limited their therapeutic and cosmeceutical applications. This study aimed to produce and characterize de novo designed antimicrobial peptides derived from WSKK11 and WSRR11 for efficacy against acne-causing bacteria. Ten designed peptides were evaluated for antimicrobial, hemolytic, and cytotoxic activities, as well as, secondary structures by FTIR and modes of action. Of the ten peptides, WKK10, WWKK11, WRR10, and WRRR11 had antimicrobial activity against Cutibacterium acnes DMST 14916 at the minimum inhibitory concentrations (MICs) of 64, 16, 32, and 32 μg/mL, respectively. The MICs of WKK10, WWKK11, WSRR10, and WRRR11 against Staphylococcus aureus TISTR 746 were 8, 4, 16, and 16 μg/mL, while those against Staphylococcus epidermidis TISTR 518 were 8, 4, 32, and 16 μg/mL, respectively. These peptides were less toxic to human erythrocytes, and WWKK11 and WRRR11 had no toxicity for MRC-5 fibroblasts, with toxicity to RAW 264.7 macrophage (≥50 μg/mL) and HaCaT keratinocyte (≥100 μg/mL). WKK10 and WRR10 were not toxic to RAW 264.7, HaCaT, and MRC-5 cells up to 100 μg/mL. Beta-sheet and alpha-helix structures of the peptides were adopted predominantly in 20 mM Tris-HCl, pH 7.4 and 50% TFE, respectively. The peptides revealed direct activity and perturbation of the cell envelope, observed by scanning electron microscopy. The results indicate that the four novel peptides, particularly WKK10 and WRR10, are promising topical antimicrobial agents for acne treatment.