Magnolol inhibits the resistance of ESBLs E. coli to fourth-generation cephalosporins in vitro and in vivo

Background Antimicrobial resistance (AMR) infection is attracting increasing attention, especially superbug infections. As a result, finding ways to reduce AMR is essential. For the time being, natural compound therapy for reducing AMR is an ideal choice. Purpose This study aims to investigate the mechanism of magnolol reducing the AMR of E. coli in vitro and vivo . Methods The morphology and function of E. coli under magnolol treatment were assessed using a scanning electron microscope, qPCR, RNA-seq, and other methods. Moreover, the in vivo treatment effects of magnolol combined with antibiotics were evaluated by HE and IHC staining. Results In this study, we found that magnolol reduced the resistance of ESBL E. coli to the fourth-generation cephalosporin in vitro via two main mechanisms. Firstly, magnolol disrupts iron ion metabolism by increasing environmental iron uptake significantly (P ≤ 0.01), leading to a significant increase in intracellular ROS (P ≤ 0.01) and membrane damage. Secondly, magnolol significantly inhibits the relative mRNA expression of blaCTX-M-1 (P ≤ 0.01) and the CTX-M-1 enzyme activity in ESBL E. coli. Furthermore, we find that magnolol can inhibit ESBL E. coli in vivo by significantly reducing the TLR4-NFκB p65 pathway ( P ≤ 0.01). Conclusion In a word, our results indicate that magnolol is a natural antibacterial adjuvant with potent inhibitory activity against bacterial resistance and exerts this activity through multiple pathways, which has particular significance for the further study of the AMR mechanism.