Berberine Attenuates Chromobacterium violaceum's Virulence by Targeting Efflux and Denitrification Machinery

Berberine is known to be a major bioactive compound from the plant Berberis aristata . As a quaternary isoquinoline alkaloid, berberine exhibits superior stability and pleiotropic antimicrobial efficacy compared to its phytochemical counterparts, owing to its unique cationic structure and multi‐targeted mechanism of action. This study evaluated the anti‐pathogenic potential of B. aristata root extract and its primary bioactive constituent, berberine, against a multidrug‐resistant (MDR) strain of Chromobacterium violaceum . Investigations utilized in vivo survival assays with the model host Caenorhabditis elegans , phenotypic characterization of virulence determinants (biofilm, hemolytic activity, efflux activity), and whole‐transcriptome sequencing to elucidate disrupted molecular pathways. Berberine demonstrated significantly higher potency than both the crude extract and six conventional antibiotics, effectively attenuating pathogen virulence and inhibiting efflux mechanisms without the induction of resistance. Transcriptomic and RT‐PCR analyses confirmed that berberine targets the bacterial denitrification pathway through the significant downregulation of nirK and norB genes. These findings advance the literature by demonstrating berberine as a useful nontraditional antibacterial agent that exerts its anti‐pathogenic effect through the simultaneous genetic and phenotypic suppression of bacterial virulence.