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Repurposing α-Adrenoreceptor Blockers as Promising Anti-Virulence Agents in Gram-Negative Bacteria

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. Bacteri...

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Autores principales: Almalki, Ahmad J., Ibrahim, Tarek S., Elhady, Sameh S., Darwish, Khaled M., Hegazy, Wael A. H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8868568/
https://www.ncbi.nlm.nih.gov/pubmed/35203781
http://dx.doi.org/10.3390/antibiotics11020178
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author Almalki, Ahmad J.
Ibrahim, Tarek S.
Elhady, Sameh S.
Darwish, Khaled M.
Hegazy, Wael A. H.
author_facet Almalki, Ahmad J.
Ibrahim, Tarek S.
Elhady, Sameh S.
Darwish, Khaled M.
Hegazy, Wael A. H.
author_sort Almalki, Ahmad J.
collection PubMed
description 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.
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spelling pubmed-88685682022-02-25 Repurposing α-Adrenoreceptor Blockers as Promising Anti-Virulence Agents in Gram-Negative Bacteria Almalki, Ahmad J. Ibrahim, Tarek S. Elhady, Sameh S. Darwish, Khaled M. Hegazy, Wael A. H. Antibiotics (Basel) Article 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. MDPI 2022-01-29 /pmc/articles/PMC8868568/ /pubmed/35203781 http://dx.doi.org/10.3390/antibiotics11020178 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Almalki, Ahmad J.
Ibrahim, Tarek S.
Elhady, Sameh S.
Darwish, Khaled M.
Hegazy, Wael A. H.
Repurposing α-Adrenoreceptor Blockers as Promising Anti-Virulence Agents in Gram-Negative Bacteria
title Repurposing α-Adrenoreceptor Blockers as Promising Anti-Virulence Agents in Gram-Negative Bacteria
title_full Repurposing α-Adrenoreceptor Blockers as Promising Anti-Virulence Agents in Gram-Negative Bacteria
title_fullStr Repurposing α-Adrenoreceptor Blockers as Promising Anti-Virulence Agents in Gram-Negative Bacteria
title_full_unstemmed Repurposing α-Adrenoreceptor Blockers as Promising Anti-Virulence Agents in Gram-Negative Bacteria
title_short Repurposing α-Adrenoreceptor Blockers as Promising Anti-Virulence Agents in Gram-Negative Bacteria
title_sort repurposing α-adrenoreceptor blockers as promising anti-virulence agents in gram-negative bacteria
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8868568/
https://www.ncbi.nlm.nih.gov/pubmed/35203781
http://dx.doi.org/10.3390/antibiotics11020178
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