Investigation of the Effect of Quercetin on the Accumulation of Ciprofloxacin Resistance in <i>Staphylococcus aureus</i>

Quinolones are one of the most widely used antibiotics globally for the treatment of <i>Staphylococcus aureus</i> infections, and resistance to their various generations of drugs occurs. The present study aimed to investigate the inhibitory effect of quercetin on quinolone-resistant <i>S. aureus</i>, triggered by efflux pumps, to assess its potential value as an efflux pump inhibitor. The minimum inhibitory concentration of ciprofloxacin for resistant bacteria was determined by the micro broth dilution method, combined with UV spectrophotometry and high-performance liquid chromatography, to observe the changes in ciprofloxacin accumulation in the antibiotic-resistant bacteria after treatment with quercetin, quantitative real-time PCR (qRT-PCR) was used to analyze the transcript levels of some efflux pump genes, finally, the whole proteins of <i>S. aureus</i> were extracted by the action of quercetin, following bicinchoninic acid (BCA) quantification, proteins were separated by SDS-PAGE, stained with Coomassie Brilliant Blue, and overall changes in total protein bands were observed. The results showed that 64-256 µg/mL quercetin significantly increased the accumulation of ciprofloxacin in antibiotic-resistant bacteria, inhibited the efflux of ciprofloxacin by 2-10-fold downregulation of the expression of the efflux pump genes <i>norA</i>, <i>norB</i>, <i>norC</i>, and <i>mepA</i>, and modulated the protein expression profile of <i>S. aureus</i>. This study revealed that quercetin has the potential to act as an efflux pump inhibitor, providing a theoretical basis for the treatment of antibiotic-resistant bacterial infections.