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  • Title: Short lipopeptides specifically inhibit the growth of Propionibacterium acnes with a dual antibacterial and anti-inflammatory action.
    Author: Yang G, Wang J, Lu S, Chen Z, Fan S, Chen D, Xue H, Shi W, He J.
    Journal: Br J Pharmacol; 2019 Jul; 176(13):2321-2335. PubMed ID: 30927447.
    Abstract:
    BACKGROUND AND PURPOSE: Propionibacterium acnes is a Gram-positive bacterium associated with the skin disorder acne. In this study, as fatty acids are considered to be important in the life habitat of P. acnes, we tested our lipopeptide library in an attempt to create potent P. acnes-specific antimicrobial agents. EXPERIMENTAL APPROACH: The antimicrobial activity of various lipopeptides was determined by measuring their minimal inhibitory concentration (MIC). Lipids from P. acnes were used to explore their mode of action. RAW264.7 cells stimulated with LPS and P. acnes respectively were used to measure their anti-inflammatory activity. Mice ears injected with P. acnes were used to assess the antimicrobial and anti-inflammatory effects of the peptides tested in vivo. KEY RESULTS: The most potent candidate, C16-KWKW, was observed to be more active against P. acnes than against other non-targeted bacterial strains, such as Streptococcus mutans, Staphylococcus aureus, and Escherichia coli. The mode of action of C16-KWKW was observed to be through interference with the integrity of the bacterial membrane, thereby impairing membrane permeability and causing leakage of inner contents of bacterial cells. Furthermore, C16-KWKW inhibited the expression of pro-inflammatory cytokines, such as IL-1β, TNF-α, and inducible NOS stimulated by both LPS and P. acnes, thus showing potential anti-inflammatory activity, which was further verified in the in vivo animal studies. CONCLUSIONS AND IMPLICATIONS: C16-KWKW is a lipopeptide displaying both anti-P. acnes and anti-inflammatory effects in vitro and in vivo and shows potential as a treatment for acne vulgaris induced by P. acnes.
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