Baicalin inhibits conjugative transfer of multidrug-resistant plasmid RP4 by regulating autoinducer-2 transporter protein LsrB

Abstract

The conjugative transfer of antibiotic resistance genes (ARGs) significantly contributes to the spread of antibiotic resistance. Quorum sensing (QS) plays a pivotal role in the regulation of this process. However, the control of conjugative transfer through quorum quenching (QQ) remains largely unexplored. In this study, a conjugative transfer model using the RP4 plasmid was constructed to investigate the effect of baicalin on conjugative transfer. The results showed that baicalin (12.5–100 μg/mL) significantly inhibited the conjugative transfer rate of the RP4 plasmid, reducing it to 1.3 × 10⁻⁴, which was only 25.8 % of the control rate. Molecular docking analyses indicated that baicalin could strongly bind to the AI-2 transporter protein LsrB, exhibiting a binding energy of −6.65 kcal/mol. An AI-2 reporter strain confirmed that baicalin interfered with the recognition process of AI-2 and blocked the QS system. Furthermore, baicalin demonstrated a significant inhibitory effect on aggregates associated with RP4 conjugative transfer. Eleven key genes related to QS, bacterial aggregation, and conjugative transfer were identified, of which nine were significantly downregulated (p < 0.05). Consequently, baicalin affected QS system activity by binding to LsrB, thereby inhibiting conjugative transfer of the RP4 plasmid. This study enhances our understanding of the mechanisms involved in conjugative transfer of ARGs, and provides a novel strategy for the prevention and control of antibiotic resistance.