Resveratrol Reverts Tolerance and Restores Susceptibility to Chlorhexidine and Benzalkonium in Gram-Negative Bacteria, Gram-Positive Bacteria and Yeasts

Abstract

The spread of microorganisms causing health-care associated infection (HAI) is contributed to by their intrinsic tolerance to a variety of biocides, used as antiseptics or disinfectants. The natural monomeric stilbenoid resveratrol (RV) is able to modulate the susceptibility to the chlorhexidine digluconate (CHX) biocide in Acinetobacter baumannii. In this study, a panel of reference strains and clinical isolates of Gram-negative bacteria, Gram-positive bacteria and yeasts were analyzed for susceptibility to CHX and benzalkonium chloride (BZK) and found to be tolerant to one or both biocides. The carbonyl cyanide m-chlorophenylhydrazine protonophore (CCCP) efflux pump inhibitor reduced the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of CHX and BZK in the majority of strains. RV reduced dose-dependently MIC and MBC of CHX and BZK biocides when used as single agents or in combination in all analyzed strains, but not CHX MIC and MBC in Pseudomonas aeruginosa, Candida albicans, Klebsiella pneumoniae, Stenotrophomonas maltophilia and Burkholderia spp. strains. In conclusion, RV reverts tolerance and restores susceptibility to CHX and BZK in the majority of microorganisms responsible for HAI. These results indicates that the combination of RV, CHX and BZK may represent a useful strategy to maintain susceptibility to biocides in several nosocomial pathogens.

Biocide resistance in Klebsiella pneumoniae: a narrative review

“…Recently, there has been demonstration of reversing biocide resistance by harnessing the synergistic activity of Resveratrol and some biocides as reported by Migliaccio et al [ 64 ], in bacteria including K. pneumoniae . Understanding biocide resistance is key in finding sustainable solutions to control biocide tolerant/resistant K. pneumoniae .…”

Resveratrol: A Review on the Biological Activity and Applications

“…A recent in vitro study highlighted that RSV, chlorhexidine digluconate (CHX), and benzalkonium chloride (BZK) co-administration could be successfully applied against nosocomial pathogens responsible for healthcare-associated infections, such as Burkholderia spp., K. pneumoniae, P. aeruginosa, Stenotrophomonas maltophilia, and Candida albicans clinical isolates [245].…”

Resveratrol as an Inhibitor of the NorA Efflux Pump and Resistance Modulator in Staphylococcus aureus

“…In S. aureus, bacteriostatic activity is described for this compound with no detection of resveratrol-induced membrane damage [19,21]. Moreover, resveratrol has increased the susceptibility of several Gram-negative and Gram-positive bacteria, including S. aureus, and yeasts to chlorhexidine and benzalkonium chloride, or to streptomycin and ciprofloxacin in multidrug-resistant Gram-negative species, and enhanced the efficacy of aminoglycosides against S. aureus, suggesting its potential as an EPI [21][22][23]. In fact, some studies report that this compound may act as an inhibitor of efflux pumps, as suggested for Escherichia coli, Acinetobacter baumannii and Arcobacter species [20,[24][25][26].…”