Characterization of the Anti-Biofilm and Anti-Quorum Sensing Activities of the β-Adrenoreceptor Antagonist Atenolol against Gram-Negative Bacterial Pathogens

The development of bacterial resistance to antibiotics is an increasing public health issue that worsens with the formation of biofilms. Quorum sensing (QS) orchestrates the bacterial virulence and controls the formation of biofilm. Targeting bacterial virulence is promising approach to overcome the resistance increment to antibiotics. In a previous detailed in silico study, the anti-QS activities of twenty-two beta-adrenoreceptor blockers were screened supposing atenolol as a promising candidate. The current study aims to evaluate the anti-QS, anti-biofilm and anti-virulence activities of the beta-adrenoreceptor blocker atenolol against Gram-negative bacteria Serratia marcescens, Pseudomonas aeruginosa, and Proteus mirabilis. An in silico study was conducted to evaluate the binding affinity of atenolol to S. marcescens SmaR QS receptor, P. aeruginosa QscR QS receptor, and P. mirabilis MrpH adhesin. The atenolol anti-virulence activity was evaluated against the tested strains in vitro and in vivo. The present finding shows considerable ability of atenolol to compete with QS proteins and significantly downregulated the expression of QS- and virulence-encoding genes. Atenolol showed significant reduction in the tested bacterial biofilm formation, virulence enzyme production, and motility. Furthermore, atenolol significantly diminished the bacterial capacity for killing and protected mice. In conclusion, atenolol has potential anti-QS and anti-virulence activities against S. marcescens, P. aeruginosa, and P. mirabilis and can be used as an adjuvant in treatment of aggressive bacterial infections.

Automated summary

The development of bacterial resistance to antibiotics is a growing public health concern exacerbated by the formation of biofilms. The study aimed to evaluate the anti-quorum sensing (QS), anti-biofilm, and anti-virulence activities of the beta-adrenoreceptor blocker atenolol against Gram-negative bacteria. In silico studies showed that atenolol had a significant binding affinity to the QS receptors of the tested bacteria. In vitro and in vivo experiments demonstrated that atenolol effectively competed with QS proteins, downregulated the expression of QS- and virulence-encoding genes, and reduced bacterial biofilm formation, virulence enzyme production, and motility. It also protected mice from bacterial infection. These findings suggest that atenolol has potential as an adjuvant in the treatment of aggressive bacterial infections.