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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...

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Autores principales: Cavalu, Simona, Elbaramawi, Samar S., Eissa, Ahmed G., Radwan, Mohamed F., S. Ibrahim, Tarek, Khafagy, El-Sayed, Lopes, Bruno Silvester, Ali, Mohamed A. M., Hegazy, Wael A. H., Elfaky, Mahmoud A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9656717/
https://www.ncbi.nlm.nih.gov/pubmed/36361877
http://dx.doi.org/10.3390/ijms232113088
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author Cavalu, Simona
Elbaramawi, Samar S.
Eissa, Ahmed G.
Radwan, Mohamed F.
S. Ibrahim, Tarek
Khafagy, El-Sayed
Lopes, Bruno Silvester
Ali, Mohamed A. M.
Hegazy, Wael A. H.
Elfaky, Mahmoud A.
author_facet Cavalu, Simona
Elbaramawi, Samar S.
Eissa, Ahmed G.
Radwan, Mohamed F.
S. Ibrahim, Tarek
Khafagy, El-Sayed
Lopes, Bruno Silvester
Ali, Mohamed A. M.
Hegazy, Wael A. H.
Elfaky, Mahmoud A.
author_sort Cavalu, Simona
collection PubMed
description 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.
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spelling pubmed-96567172022-11-15 Characterization of the Anti-Biofilm and Anti-Quorum Sensing Activities of the β-Adrenoreceptor Antagonist Atenolol against Gram-Negative Bacterial Pathogens Cavalu, Simona Elbaramawi, Samar S. Eissa, Ahmed G. Radwan, Mohamed F. S. Ibrahim, Tarek Khafagy, El-Sayed Lopes, Bruno Silvester Ali, Mohamed A. M. Hegazy, Wael A. H. Elfaky, Mahmoud A. Int J Mol Sci Article 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. MDPI 2022-10-28 /pmc/articles/PMC9656717/ /pubmed/36361877 http://dx.doi.org/10.3390/ijms232113088 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
Cavalu, Simona
Elbaramawi, Samar S.
Eissa, Ahmed G.
Radwan, Mohamed F.
S. Ibrahim, Tarek
Khafagy, El-Sayed
Lopes, Bruno Silvester
Ali, Mohamed A. M.
Hegazy, Wael A. H.
Elfaky, Mahmoud A.
Characterization of the Anti-Biofilm and Anti-Quorum Sensing Activities of the β-Adrenoreceptor Antagonist Atenolol against Gram-Negative Bacterial Pathogens
title Characterization of the Anti-Biofilm and Anti-Quorum Sensing Activities of the β-Adrenoreceptor Antagonist Atenolol against Gram-Negative Bacterial Pathogens
title_full Characterization of the Anti-Biofilm and Anti-Quorum Sensing Activities of the β-Adrenoreceptor Antagonist Atenolol against Gram-Negative Bacterial Pathogens
title_fullStr Characterization of the Anti-Biofilm and Anti-Quorum Sensing Activities of the β-Adrenoreceptor Antagonist Atenolol against Gram-Negative Bacterial Pathogens
title_full_unstemmed Characterization of the Anti-Biofilm and Anti-Quorum Sensing Activities of the β-Adrenoreceptor Antagonist Atenolol against Gram-Negative Bacterial Pathogens
title_short Characterization of the Anti-Biofilm and Anti-Quorum Sensing Activities of the β-Adrenoreceptor Antagonist Atenolol against Gram-Negative Bacterial Pathogens
title_sort characterization of the anti-biofilm and anti-quorum sensing activities of the β-adrenoreceptor antagonist atenolol against gram-negative bacterial pathogens
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9656717/
https://www.ncbi.nlm.nih.gov/pubmed/36361877
http://dx.doi.org/10.3390/ijms232113088
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