Antibacterial activity of long-chain polyunsaturated fatty acids against Propionibacterium acnes and Staphylococcus aureus

Andrew P Desbois, Keelan C Lawlor, Andrew P Desbois, Keelan C Lawlor

Abstract

New compounds are needed to treat acne and superficial infections caused by Propionibacterium acnes and Staphylococcus aureus due to the reduced effectiveness of agents used at present. Long-chain polyunsaturated fatty acids (LC-PUFAs) are attracting attention as potential new topical treatments for Gram-positive infections due to their antimicrobial potency and anti-inflammatory properties. This present study aimed to investigate the antimicrobial effects of six LC-PUFAs against P. acnes and S. aureus to evaluate their potential to treat infections caused by these pathogens. Minimum inhibitory concentrations were determined against P. acnes and S. aureus, and the LC-PUFAs were found to inhibit bacterial growth at 32-1024 mg/L. Generally, P. acnes was more susceptible to the growth inhibitory actions of LC-PUFAs, but these compounds were bactericidal only for S. aureus. This is the first report of antibacterial activity attributed to 15-hydroxyeicosapentaenoic acid (15-OHEPA) and 15-hydroxyeicosatrienoic acid (HETrE), while the anti-P. acnes effects of the six LC-PUFAs used herein are novel observations. During exposure to the LC-PUFAs, S. aureus cells were killed within 15-30 min. Checkerboard assays demonstrated that the LC-PUFAs did not antagonise the antimicrobial potency of clinical agents used presently against P. acnes and S. aureus. However, importantly, synergistic interactions against S. aureus were detected for combinations of benzoyl peroxide with 15-OHEPA, dihomo-γ-linolenic acid (DGLA) and HETrE; and neomycin with 15-OHEPA, DGLA, eicosapentaenoic acid, γ-linolenic acid and HETrE. In conclusion, LC-PUFAs warrant further evaluation as possible new agents to treat skin infections caused by P. acnes and S. aureus, especially in synergistic combinations with antimicrobial agents already used clinically.

Figures

Figure 1
Figure 1
Killing kinetics of six LC-PUFAs against a S. aureus ATCC43300 inoculum of ~2.6 × 105 colony forming unit (CFU)/mL in phosphate-buffered saline (PBS) showing that each LC-PUFA killed the bacteria rapidly. n = 3; mean ± one standard deviation (not all error bars are visible). Please note that a single kill curve is shown for DHA, EPA, HETrE and 15-OHEPA because the values were identical and the kill curves overlapped exactly.
Figure 2
Figure 2
Molecular structures of the six LC-PUFAs used in this present study. All double bonds are in cis orientation except for the n-7 bonds of 15-HETrE and 15-OHEPA that are in trans orientation.

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