Temporin-GHa derived peptide shows inhibitory efficacy against Cutibacterium acnes and alleviates inflammatory reactions in acne vulgaris

Acne vulgaris is a widespread chronic inflammatory skin disease that is mainly caused by Cutibacterium acnes infection and subsequent inflammation. Temporin-GHaR4G7R (GHaR4G7R) was derived from Temporin-GHa of frog Hylarana guentheri. Its antibacterial performance against C. acnes and potential mechanism against acne vulgaris in vitro and in vivo were evaluated. In vitro tests demonstrated that GHaR4G7R displayed potent bactericidal effects against C. acnes, with both the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 3.1 μM. It exerted antibacterial effect by disrupting the bacterial membranes, accompanied by low propensity for developing drug resistance. GHaR4G7R significantly inhibited the formation of early biofilms and eliminated established biofilms of C. acnes by decreasing exopolysaccharide synthesis. Meanwhile, GHaR4G7R demonstrated an anti-inflammatory effect on HaCaT cells challenged with heat-inactivated C. acnes by significantly down-regulating the expression of TLR2/NF-κB/MAPK pathway-associated proteins by qRT-PCR, immunofluorescence, and Western blot assays. As expected, GHaR4G7R significantly decreased the bacterial colonization in rat ear model induced by C. acnes, and relieved the auricular swelling and inflammatory cell infiltration through inhibiting the TLR2/NF-κB/MAPK signaling pathway, leading to down-regulation of the inflammatory cytokine expression and alleviation of the skin inflammation in vivo. The research indicates that GHaR4G7R might be a potential alternative for developing novel strategies for treating acne vulgaris.