Short lipopeptides specifically inhibit the growth of Propionibacterium acnes with dual antibacterial and anti-inflammatory action.

ABSTRACT: BACKGROUND AND PURPOSE:Propionibacterium acnes (P. acnes) is a Gram-positive bacterium associated with the skin disorder acne. In this study, we determined the importance of fatty acids 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:Antimicrobial activity was determined by the minimal inhibitory concentration (MIC). Lipids from P. acnes were used to explore the mode of action. RAW264.7 cells respectively stimulated with LPS and P. acnes were used to measure the 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, with an MIC of 2 ?g·ml-1 , 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 bacterial membrane, thereby impairing membrane permeability and causing leakage of the inner contents of bacterial cells. In addition, C16-KWKW inhibited the expression of pro-inflammatory cytokines, such as IL-1?, TNF-?, and inducible NOS, stimulated by both LPS and P. acnes, thus showing potential anti-inflammatory activity, which was further assessed in animal studies in vivo. CONCLUSIONS AND IMPLICATIONS:C16-KWKW is a lipopeptide displaying both anti-P. acnes and anti-inflammatory effects in vitro and in vivo, and exhibits potential as a treatment for acne vulgaris induced by P. acnes.

SUBMITTER: Yang G 

PROVIDER: S-EPMC6514292 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature