Farnesol in combination with N-acetylcysteine against Staphylococcus epidermidis planktonic and biofilm cells

Abstract

Staphylococcus epidermidis is the most frequent cause of nosocomial sepsis and catheter-related infections, in which biofilm formation is considered to be the main virulence mechanism. In biofilm environment, microbes exhibit enhanced resistance to antimicrobial agents. This fact boosted the search of possible alternatives to antibiotics. Farnesol and N-acetylcysteine (NAC) are non-antibiotic drugs that have demonstrated antibacterial properties. In this study, the effect of farnesol and NAC isolated or in combination (farnesol+NAC) was evaluated. NAC at 10 × MIC caused a total cell death in planktonic cells.On the other hand, S. epidermidis biofilms exhibited 4 log reduction in viable cell number after a 24h treatment with NAC at the former concentration. Our results demonstrated that there was a higher CFU log reduction of S. epidermidis planktonic cells when farnesol was combined with NAC at 1 × MIC relatively to each agent alone. However, these results were not relevant because NAC alone at 10 × MIC was always the condition which gave the best results, having a very high killing effect on planktonic cells and a significant bactericidal effect on biofilm cells. This study demonstrated that no synergy was observed between farnesol and NAC. However, the pronounced antibacterial effect of NAC against S. epidermidis, on both lifestyles, indicates the use of NAC as a potential therapeutic agent in alternative to antibiotics.

Confocal laser scanning microscopy analysis of S. epidermidis biofilms exposed to farnesol, vancomycin and rifampicin

“…We have recently shown that farnesol increased cell death by the action of tetracycline or rifampicin [20], possibly due to the permeabilization of the cell wall [22]. The same was true in combination with N -acetylcysteine [27]. However, the exact mechanism of farnesol action in S. epidermidis is not fully known.…”

Antibacterial effect of N‐acetylcysteine and taurolidine on planktonic and biofilm forms of Enterococcus faecalis

“…In addition to its antibacterial activity against planktonic bacteria, NAC is a mucolytic agent that acts against biofilms by reducing the production of extracellular polysaccharide and adhesion of bacteria on surfaces . The antibiofilm activity of NAC against several microbial biofilms has been demonstrated in the medical literature . Recently, Quah et al.…”

“…In addition to its antibacterial activity against planktonic bacteria, NAC is a mucolytic agent that acts against biofilms by reducing the production of extracellular polysaccharide and adhesion of bacteria on surfaces (27,28). The antibiofilm activity of NAC against several microbial biofilms has been demonstrated in the medical literature (27)(28)(29)(30). Recently, Quah et al (7) reported that NAC was effective against both the planktonic and biofilm forms of E. faecalis at pH 11 and that the presence of dentin powder did not reduce its antibacterial activity for up to 14 days.…”

CORR Insights®: d-amino Acid Inhibits Biofilm but not New Bone Formation in an Ovine Model

“…Increasing evidence also suggests that antibiotics may be a necessary addition to ensure elimination of contamination [3,4,6]. While reduction in biofilm biomass was observed using DAAs alone, complete eradication was not observed even at the highest concentrations studied.…”

“…D-amino acids (D-AAs), cis 2-decenoic acid, and farnesol are among these recently discovered biofilm inhibitors that have been shown to prevent biofilm formation, disperse existing biofilm, and revert persister cells to a more active and antimicrobial-susceptible state [4,7,8] Recent studies of antiinfective strategies for implanted materials have highlighted the need for inclusion of biofilm-targeting therapy in addition to antibiotics [1,5]. In the study by Harmata and colleagues, the specific inhibition and dispersal of both methicillin-susceptible and methicillin resistant Staphylococcus aureus strains were confirmed at particular D-AA concentrations.…”