Combining with matrine restores ciprofloxacin efficacy against qnrS producing E. coli in vitro and in vivo.

The exposure risk of plasmid-mediated quinolone resistance (PMQR) genes increases the incidence of resistant bacterial infections, has resulted in clinical treatment failures with ciprofloxacin, necessitating urgent implementation of novel strategies for controlling this situation. Matrine serves as the principal constituent of the traditional Chinese herb Sophora flavescens Ait. and exhibits pharmacological activities including anti-inflammatory, antibacterial, anti-tumor, and hepatoprotective effects. However, the precise mechanism by which matrine exhibits antibacterial activity remains incompletely elucidated. This study investigated the antibacterial potential and synergistic mechanism of matrine in combination with ciprofloxacin against qnrS-carrying E. coli. The clinical ciprofloxacin-resistant E. coli carrying the qnrS and the recombinant E. coli DE3 (pET28a-qnrS) were evaluated for their antibacterial activity in vitro, it was found that the combination of matrine/ciprofloxacin exhibited a significant synergistic, reducing the MIC value of ciprofloxacin against qnrS-positive E. coli by 4-fold, and it effectively reduced the bacterial load to undetectable levels within 10 h without obvious cytotoxicity. Moreover, consistent findings were observed in significantly reducing bacterial load within the mouse infection model. Molecular docking revealed that matrine was localized in the large loop B of the qnrS crystal structure, establishing hydrogen bonds with Thr-102 and Arg-101, thereby disrupting the activity of qnrS. Interaction analysis further confirmed that matrine could significantly inhibit the protective effect of qnrS on gyrase and restore the activity of ciprofloxacin against qnrS-positive E. coli. Matrine may serve as a qnrS inhibitor to restore the efficacy of ciprofloxacin, suggesting its potential as a novel antibiotic adjuvant for controlling bacterial infections.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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