Inhibition of the norA gene expression and the NorA efflux pump by the tannic acid

Sci Rep. 2023 Oct 13;13(1):17394. doi: 10.1038/s41598-023-43038-5.

Abstract

The NorA efflux pump of Staphylococcus aureus is known to play a major role in the development of resistance against quinolone drugs by reducing their concentration inside target pathogens. The objective of this study was to evaluate the ability of tannic acid to inhibit the gene expression of the NorA efflux pump in Staphylococcus aureus and to evaluate the in silico effect on the pump. Efflux pump inhibition was evaluated by fluorimetry. The checkerboard method evaluates the effect of the test substance in combination with an antimicrobial at different concentrations. To gene expression evaluation NorA the assay was performed using: a sub-inhibitory concentration preparation (MIC/4) of the antibiotic; a sub-inhibitory concentration preparation (MIC/4) of the antibiotic associated with tannic acid at a sub-inhibitory concentration (MIC/4). In this study, docking simulations were performed by the SWISSDOCK webserver. The ability of tannic acid to inhibit the NorA efflux pump can be related to both the ability to inhibit the gene expression of this protein, acting on signaling pathways involving the ArlRS membrane sensor. As well as acting directly through direct interaction with the NorA protein, as seen in the approach and in silico and in vitro per checkerboard method and fluorimetry of bromide accumulated in the cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / metabolism
  • Ciprofloxacin* / pharmacology
  • Gene Expression
  • Humans
  • Microbial Sensitivity Tests
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / metabolism
  • Staphylococcal Infections*
  • Staphylococcus aureus
  • Tannins / metabolism
  • Tannins / pharmacology

Substances

  • Ciprofloxacin
  • Tannic Acid
  • Anti-Bacterial Agents
  • Tannins
  • Bacterial Proteins
  • Multidrug Resistance-Associated Proteins