Berberine: A Natural pqs System Inhibitor in Pseudomonas aeruginosa for Foodborne Infection Control

Pseudomonas aeruginosa poses a significant threat to food safety. The P. aeruginosa pqs 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 pqs system inhibitor. Berberine reduced P. aeruginosa 2-heptyl-3-hydroxy-4(1H)-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 pqs 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 P. aeruginosa-induced plant tissue decay and bacterial damage in human cells. These findings establish berberine as a potent pqs inhibitor that targets PqsR, underscoring its potential for controlling food spoilage and contamination risk.