Abstract
Antimicrobial resistance is among the world’s most urgent public health problems. Diminishing of the virulence of bacteria is a promising approach to decrease the development of bacterial resistance. Quorum sensing (QS) systems orchestrate the bacterial virulence in inducer–receptors manner. Bacteria can spy on the cells of the host by sensing adrenergic hormones and other neurotransmitters, and in turn, these neurotransmitters can induce bacterial pathogenesis. In this direction, α-adrenergic blockers were proposed as an anti-virulence agents through inhibiting the bacterial espionage. The current study aimed to explore the α-blockers’ anti-QS activities. Within comprehensive in silico investigation, the binding affinities of seven α-adrenoreceptor blockers were evaluated towards structurally different QS receptors. From the best docked α-blockers into QS receptors, terazosin was nominated to be subjected for further in vivo and in vitro anti-QS and anti-virulence activities against Chromobacterium violaceum and Pseudomonas aeruginosa. Terazosin showed a significant ability to diminish the QS-controlled pigment production in C. violaceum. Moreover, Terazosin decreased the P. aeruginosa biofilm formation and down-regulated its QS-encoding genes. Terazosin protected mice from the P. aeruginosa pathogenesis. In conclusion, α-adrenergic blockers are proposed as promising anti-virulence agents as they hinder QS receptors and inhibit bacterial espionage.
Highlights
Publisher’s Note: MDPI stays neutralDrug repurposing is discovering new applications of the well-known drugs which are known for specific clinical use
Validating the second sophisticated docking protocol was proceeded through performing self-docking of the co-crystalline ligands by adopting the same docking procedure and, in a fashion, which are comparable to those reported by respected studies [42,43]
Targeting bacterial virulence strategy confers multiple benefits, especially if safe drugs are used for this purpose [1,2,11]
Summary
Publisher’s Note: MDPI stays neutralDrug repurposing is discovering new applications of the well-known drugs which are known for specific clinical use. Re-evaluating the medical use of already-permitted safe drugs has gained increasing interest as a promising strategy that acquires different merits These advantages include saving time and costs to carry out further pharmaceutical, pharmacological, and toxicological studies for already-approved safe drugs [1,2,3]. Inverse molecular docking is a highly recognized approach that has been widely used to identify multiple putative biological targets, to which small drug-like molecules are able to bind or even weakly bind [4]. The application of this in silico tool has been considered beneficial for facilitating drug design and discovery. A putative ligand–target inverse docking can predict potential biological targets with possible correlation to the observed drug candidate’s with regard to jurisdictional claims in published maps and institutional affiliations
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