Evaluation of antibacterial activity and reversal of the NorA and MepA efflux pump of estragole against Staphylococcus aureus bacteria

Arch Microbiol. 2021 Aug;203(6):3551-3555. doi: 10.1007/s00203-021-02347-x. Epub 2021 May 3.

Abstract

The antibacterial activity of the monoterpene estragole was evaluated against two strains of bacteria with an efflux pump mechanism, which are Staphylococcus aureus 1199B and S. aureus K2068, which have a NorA and MepA pump, respectively. For that, the methodology proposed by CLSI with modifications was followed, and to evaluate the reversal of the efflux pump, subinhibitory concentrations (MIC/8) of estragole and standard pump inhibitors, CCCP and Chlorpromazine were used and it was verified whether they managed to modulate the action of Norfloxacin, Ciprofloxacin and Ethidium Bromide, an indicator of an efflux pump. It was observed that estragole positively modulated norfloxacin and ethidium bromide against the strain of S. aureus 1199B and that it also managed to reduce the MIC of ethidium bromide against the strain of S. aureus K2068. In the non-clinical acute toxicity tests with estragole, the animals treated with the dose of 625 mg/kg/v.o. showed no clinical signs of toxicity, according to the parameters evaluated. These results are promising, since it places estragole as a possible inhibitor of the efflux pump, thus managing to inhibit this mechanism of action in the strains tested.

Keywords: Bacterial resistance; Efflux pump; Estragole; Terpenes.

MeSH terms

  • Allylbenzene Derivatives* / pharmacology
  • Animals
  • Anisoles* / pharmacology
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / metabolism
  • Endopeptidases / metabolism
  • Microbial Sensitivity Tests
  • Multidrug Resistance-Associated Proteins / metabolism
  • Staphylococcus aureus* / drug effects
  • Staphylococcus aureus* / metabolism

Substances

  • Allylbenzene Derivatives
  • Anisoles
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Multidrug Resistance-Associated Proteins
  • NorA protein, Staphylococcus
  • estragole
  • Endopeptidases