Inhibition of biofilm formation and quorum sensing mediated phenotypes by berberine in Pseudomonas aeruginosa and Salmonella typhimurium

Abstract

Quorum sensing is involved in biofilm formation and modulates virulence factor production in pathogenic bacteria. Quorum sensing inhibitors can be used as novel intervention strategies for attenuating bacterial pathogenicity. Berberine is an isoquinoline alkaloid with pharmacological properties. The present study investigated the sub-inhibitory concentrations of berberine for inhibiting biofilm formation and quorum sensing regulated phenotypes in the bacterial pathogens Pseudomonas aeruginosa PA01 and Salmonella enterica serovar Typhimurium. Berberine inhibited quorum sensing regulated violacein production in C. violaceum. It reduced the pigment production in the wild type strain at 1.6 mg mL⁻¹ by 62.67%. In the opportunistic pathogen, P. aeruginosa PA01, at sub-MIC, it showed significant antibiofilm activity in by reducing biomass by 71.70% (p < 0.05). It prevented biofilm formation and inactivated biofilm maturation in bacterial pathogens at the concentration ranging from 0.019 to 1.25 mg mL⁻¹. In silico studies showed that berberine interacted with the quorum sensing signal receptors, LasR and RhlR. Furthermore, its anti-infective properties in S. Typhimurium were studied. At sub-inhibitory concentrations of 0.019 mg mL⁻¹, it reduced biofilm formation in S. Typhimurium by 31.20%. It significantly prevented invasion and adhesion of Salmonella invasion in the colonic cell, HT 29 by 55.37% and 54.68%, respectively. It was capable of reducing in vivo virulence in Caenorhabditis elegans infected with Salmonella at 0.038 mg mL⁻¹ by 65.38%. Our results suggest that berberine, previously recognised for its antimicrobial activity, could find potential application as an anti-biofilm and anti-infective agent based on its quorum sensing inhibitory activity.