RecO : A Potential target for Overcoming Fluoroquinolone Resistance in Pasteurella multocida

Abstract Aims Pasteurella multocida (Pm) is one of the main pathogens causing bovine respiratory disease in China. The prevention and control measures against Pm are traditionally based on the use of broad-spectrum antibiotics. Previous studies have found that Pm is prone to developing antibiotic resistance and tolerance-related mutations when exposed to low concentrations of antibiotics, ultimately leading to challenges in the prevention and control of Pm. This study aimed to explore the role of the recO gene in Pm in mediating resistance and tolerance to fluoroquinolones. Methods and Results Highly pathogenic Pm strains (fluoroquinolone-sensitive P3; enrofloxacin-induced resistant P32) were used. RNA-seq screened SOS response-related differentially expressed genes, with recO functionally verified. Its role in Pm’s fluoroquinolone resistance/tolerance was clarified via MIC, MBC.The results showed that recO deletion reduced the bacterial tolerance by approximately 10–100-fold after 4 h of exposure to enrofloxacin (ENR) (p 0.05), decreased the MBC value by 2-fold, and significantly prolonged the time required for resistance development. Conclusions In conclusion, inhibiting the expression of the recO gene in Pm not only reduces its resistance to fluoroquinolones but also delays the development of fluoroquinolone resistance. It is hypothesized that the recO gene could serve as a potential target for enhancing the efficacy of fluoroquinolones, thereby improving their antibacterial activity against Pm.