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

Abstract

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 β-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 β-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.

Dronedarone Enhances the Antibacterial Activity of Polymyxin B and Inhibits the Quorum Sensing System by Interacting with LuxS

“…25−30 The ability of β-adrenoreceptor antagonists or blockers to inhibit the QS system has been demonstrated by previous studies. 13,14,31 However, the target of QS suppression was not been identified.…”

“…Dronedarone blocks potassium, sodium, and L-type calcium currents and exerts antiadrenergic effects by noncompetitive binding to β-adrenergic receptors . However, when nonantibiotic drugs are used as antibiotic potentiators, their mechanisms of action are usually different from their original pharmacological effects. − The ability of β-adrenoreceptor antagonists or blockers to inhibit the QS system has been demonstrated by previous studies. ,, However, the target of QS suppression was not been identified.…”

Controlling of Bacterial Virulence: Evaluation of Anti-Virulence Activities of Prazosin against Salmonella enterica

“…In previous studies, adrenoreceptor antagonists were screened for their anti-QS and anti-virulence activities [ 31 , 32 ]. Interestingly, β-adrenoreceptor antagonists atenolol and metoprolol diminished the virulence of Pseudomonas aeruginosa, Proteus mirabilis , Serratia marcescens, Salmonella enterica , and E. coli [ 32 , 60 , 61 ]. In addition, α-adrenoreceptor blocker antagonist terazosin showed significant in vitro and in vivo reduction in S. enterica and P. aeruginosa pathogenesis [ 19 , 31 ].…”

Resistance, Tolerance, Virulence and Bacterial Pathogen Fitness—Current State and Envisioned Solutions for the Near Future

“…The authors proved the ability of atenolol to reduce the biofilm formation, virulence enzyme production and motility and finally its potential to protect infected mice. They concluded that atenolol exerts anti-QS and antivirulence activities and can be used as a complementary/adjuvant anti-infectious drug [ 268 ].…”