Antibiofilm activities of fatty acids including myristoleic acid against Cutibacterium acnes via reduced cell hydrophobicity

Background: Cutibacterium acnes is a major colonizer and inhabitant of human skin and contributes to the pathogenesis of acne vulgaris. C. acnes either alone or with Staphylococcus aureus, which also inhabits skin, readily forms biofilms that are often tolerant of conventional antibiotics and the host immune system. It was hypothesized that the amphiphilic nature of some fatty acids (FAs) inhibit C. acnes or mixed biofilm formation. Purpose: The antibacterial and antibiofilm activities of 24 saturated and unsaturated FAs were investigated against C. acnes as well as a mixture of the bacteria C. acnes and S. aureus. Methods: Anti-biofilm assays, antimicrobial assays, confocal laser scanning microscopy, scanning electron microscopy, extracellular polymeric substance production, and microbial adherence to hydrocarbon assay were utilized to elucidate how active FAs influence biofilm development. Results: Seventeen FAs at 20 mu g/ml inhibited C. acnes biofilm formation by 60-99%. The minimum inhibitory concentrations (MICs) of 20 FAs were >= 500 mu g/ml but 4 medium-chain FAs had MICs in a range 15 to 200 mu g/ ml. Interestingly, myristoleic acid inhibited biofilm formation at 1 mu g/ml. Myristoleic acid also inhibited the formation of S. aureus and mixed C. acnes/S. aureus biofilms. FAs reduced C. acnes hydrophobicity and we found this was generally correlated with their antibiofilm forming efficacies. Transcriptional analyses showed that myristoleic acid modulates the expression of several biofilm-related genes such as lipase, hyaluronate lyase, and virulence-related genes. Conclusion: This study shows myristoleic acid and other FAs inhibit biofilm formation by C. acnes and mixed biofilm formation by C. acnes and S. aureus. Hence, myristoleic acid might be useful for treating or preventing acne and C. acnes associated diseases.