Effect of Farnesol on Staphylococcus aureus Biofilm Formation and Antimicrobial Susceptibility

Abstract

Staphylococcus aureus is among the leading pathogens causing bloodstream infections able to form biofilms on host tissue and indwelling medical devices and to persist and cause disease. Infections caused by S. aureus are becoming more difficult to treat because of increasing resistance to antibiotics. In a biofilm environment particularly, microbes exhibit enhanced resistance to antimicrobial agents. Recently, farnesol was described as a quorum-sensing molecule with possible antimicrobial properties. In this study, the effect of farnesol on methicillin-resistant and -susceptible strains of S. aureus was investigated. With viability assays, biofilm formation assessment, and ethidium bromide uptake testing, farnesol was shown to inhibit biofilm formation and compromise cell membrane integrity. The ability of farnesol to sensitize S. aureus to antimicrobials was assessed by agar disk diffusion and broth microdilution methods. For both strains of staphylococci, farnesol was only able to reverse resistance at a high concentration (150 M). However, it was very successful at enhancing the antimicrobial efficacy of all of the antibiotics to which the strains were somewhat susceptible. Therefore, synergy testing of farnesol and gentamicin was performed with static biofilms exposed to various concentrations of both agents. Plate counts of harvested biofilm cells at 0, 4, and 24 h posttreatment indicated that the combined effect of gentamicin at 2.5 times the MIC and farnesol at 100 M (22 g/ml) was able to reduce bacterial populations by more than 2 log units, demonstrating synergy between the two antimicrobial agents. This observed sensitization of resistant strains to antimicrobials and the observed synergistic effect with gentamicin indicate a potential application for farnesol as an adjuvant therapeutic agent for the prevention of biofilm-related infections and promotion of drug resistance reversal.

Effect of Farnesol on Planktonic and Biofilm Cells of Staphylococcus epidermidis

“…These data indicated that low concentrations of farnesol were sufficient to exhibit antibacterial effect, as was demonstrated by viability assays. For Staphylococcus aureus this was observed in the presence of 200 lM (44 lg ml -1 ) farnesol [6]. This inhibitory effect can be due to the hydrophobic nature of farnesol that favours its accumulation in the membrane, possibly causing membrane disruption [6].…”

“…For Staphylococcus aureus this was observed in the presence of 200 lM (44 lg ml -1 ) farnesol [6]. This inhibitory effect can be due to the hydrophobic nature of farnesol that favours its accumulation in the membrane, possibly causing membrane disruption [6]. In fact, exposure to terpene alcohols has been recently shown to affect the cell membranes of S. aureus, Escherichia coli and Listeria monocytogenes, resulting in leakage of K ?…”

“…Specifically, farnesol has been reported to have antibacterial properties. For instance, in Streptococcus mutans, brief exposure to farnesol affected growth and metabolism by disrupting the bacterial membrane, as well as the accumulation and polysaccharide content of biofilms of the streptococci [6]. In Staphylococcus aureus, farnesol was shown to inhibit biofilm F. I.…”

“…However, a more important consequence of biofilm formation, with profound clinical implications is the markedly enhanced resistance to antimicrobial agents by biofilm-associated microorganisms, which are estimated to be 50-500 times more resistant than their planktonic counterparts [6]. The ability of biofilm-embedded cells to resist to antimicrobial agents points to the importance of a continuous search for novel agents that are effective against bacteria in this mode of growth or that can work in synergy with the currently available myriad of antimicrobial agents [6]. Several studies have been assessing the antimicrobial potential of natural terpene alcohols.…”

“…In Staphylococcus aureus, farnesol was shown to inhibit biofilm F. I. A. Gomes Á P. Teixeira Á J. Azeredo Á R. Oliveira (&) IBB-Institute for Biotechnology and Bioengineering, Centre of Biological Engineering, University of Minho, Campus de Gualtar, Braga 4710-057, Portugal e-mail: roliveira@deb.uminho.pt formation and compromise cell membrane integrity [6]. Inoue et al [4] also demonstrated that farnesol have antibacterial activity against S. aureus.…”