RecA inhibitor epicatechin prolongs the development of fluoroquinolone resistance in Pasteurella multocida

Pasteurella multocida (P. multocida), a primary pathogen of bovine respiratory diseases, has become resistant to many antibiotics, including fluoroquinolones and aminoglycosides. A large number of studies have proved that SOS reaction plays a crucial role in the development of antibiotic resistance. We have shown that the deletion of SOS response-related genes (recA, recO) can delay the development of fluoroquinolone resistance in P. multocida, therefore, it can be used as potential targets for antibiotic resistance inhibitors. In this study, we have used molecular docking to screen RecA protein inhibitors with high throughput screening, and found that epicatechin as an inhibitor significantly inhibited the formation of fluoroquinolone resistance in P. multocida, while in vitro coadministration of epicatechin with and without ciprofloxacin improved the efficacy of the antimicrobial agent. In conclusion, our results indicate that epicatechin is an efficient RecA inhibitor, implying that combining it with ciprofloxacin is a highly promising method for treating P. multocida resistant to fluoroquinolones.