Novel-designed antimicrobial peptides with dual antimicrobial and anti-inflammatory actions against Cutibacterium acnes for acne vulgaris therapy

Acne vulgaris is a prevalent skin condition among adolescents, primarily instigated by over-colonization and subsequent inflammation triggered by Cutibacterium acnes. Although topical and oral antibiotics are standard treatments, they often lead to the proliferation of antibiotic-resistant bacteria and are associated with undesirable side effects. Antimicrobial peptides (AMPs) are considered a promising solution to these challenges. In this study, we aimed to develop novel short AMPs to combat C. acnes. By comparing sequences and abstracting the distribution of residue types of established AMPs, we derived a sequence template. Using this template, we crafted novel anti-C. acnes peptides comprising 13 amino acid residues. To enhance their potential therapeutic application, we designed a series of peptides by varying the number and position of the tryptophan residues. Among these peptides, DAP-7 and DAP-10 demonstrated potent antimicrobial activity against both antibiotic-susceptible and -resistant strains of C. acnes, with minimal cytotoxicity. The antimicrobial action of these peptides was attributed to their ability to target the bacterial membrane, resulting in permeabilization and rupture. Moreover, DAP-7 and DAP-10 effectively reduced the expression of pro-inflammatory cytokines induced by C. acnes and remained stable for up to 12 h after exposure to proteases found in acne lesions. Notably, DAP-7 decreased the C. acnes colonies on the ears and significantly alleviated C. acnes-induced ear swelling in a mouse model. Our findings suggest that the DAP-7 and DAP-10 peptides hold promise as candidates for developing a new acne vulgaris treatment.