Berberine: A Natural <i>pqs</i> System Inhibitor in <i>Pseudomonas aeruginosa</i> for Foodborne Infection Control

<i>Pseudomonas aeruginosa</i> poses a significant threat to food safety. The <i>P. aeruginosa</i> <i>pqs</i> quorum sensing system regulates spoilage potential. Using natural QS-targeting compounds to attenuate virulence represents a promising approach to mitigating bacterial contamination and spoilage. This study screened traditional Chinese medicine monomers and identified berberine as a <i>pqs</i> system inhibitor. Berberine reduced <i>P. aeruginosa</i> 2-heptyl-3-hydroxy-4(1<i>H</i>)-quinolone (PQS) production, pyocyanin biosynthesis, biofilm formation, and motility without affecting bacterial growth. Genetic analysis revealed that berberine targets transcriptional regulator PqsR to suppress the <i>pqs</i> system in a dose-dependent manner. Structural modeling predicted a direct interaction between berberine and PqsR, as confirmed by microscale thermophoresis. Site-directed mutagenesis identified Ile236 as the key residue mediating this interaction. In infection models, berberine treatment mitigated <i>P. aeruginosa</i>-induced plant tissue decay and bacterial damage in human cells. These findings establish berberine as a potent <i>pqs</i> inhibitor that targets PqsR, underscoring its potential for controlling food spoilage and contamination risk.