International Journal of Molecular Sciences · 2022 · 50 citations · 77 references
Life SciencesMicrobiologyPharmacologyAntimicrobial PharmacologyAntimicrobial PharmacotherapyAntimicrobial ResistanceAntibacterial AgentsAntibacterial PharmacologyAntibiotic ResistanceBacterial Virulence FactorsQuorum SensingResistance In Gram-negative BacteriaAnti-biofilm StrategiesBacterial Biofilm AccumulationBacterial Biofilm ControlBacterial Biofilm EffectsBiofilm-disrupting AgentsPseudomonas Aeruginosa ResistanceQuorum Sensing InhibitionQuorum Sensing Inhibitors
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.
77
SWISS-MODEL: homology modelling of protein structures and complexes
Andrew Waterhouse, Martino Bertoni, Stefan Bienert et al. · Nucleic Acids Research · 2018 · 13.6K citations · Full text
CASTp 3.0: computed atlas of surface topography of proteins
Wei Tian, Chang Chen, Xue Lei et al. · Nucleic Acids Research · 2018 · 2.4K citations · Full text
The SWISS-MODEL Repository—new features and functionality
Stefan Bienert, Andrew Waterhouse, Tjaart de Beer et al. · Nucleic Acids Research · 2016 · 1.8K citations · Full text
CASTp: Computed Atlas of Surface Topography of proteins
T.A. Binkowski · Nucleic Acids Research · 2003 · 1.7K citations · Full text