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

• Published in: Scientific reports Vol. 13; no. 1; p. 17394
• Main Authors: Tintino, Saulo Relison, Wilairatana, Polrat, de Souza, Veruska Cintia Alexandrino, da Silva, Julia Mariana Assis, Pereira, Pedro Silvino, de Morais Oliveira-Tintino, Cícera Datiane, de Matos, Yedda Maria Lobo Soares, Júnior, João Tavares Calixto, de Queiroz Balbino, Valdir, Siqueira-Junior, José P., Menezes, Irwin Rose Alencar, Siyadatpanah, Abolghasem, Coutinho, Henrique Douglas Melo, Balbino, Tereza Cristina Leal
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13-10-2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/326/22/1434; 631/45/612/1237; Acids; Antibiotics; Drug development; Drug resistance; Gene expression; Humanities and Social Sciences; Minimum inhibitory concentration; multidisciplinary; NorA protein; Science; Science (multidisciplinary); Staphylococcus aureus; Tannic acid
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-43038-5

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.