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Unlocking the Antibiofilm Potential of Natural Compounds by Targeting the NADH:quinone Oxidoreductase WrbA

Biofilm-dwelling cells endure adverse conditions, including oxidative imbalances. The NADH:quinone oxidoreductase enzyme WrbA has a crucial role in the mechanism of action of antibiofilm molecules such as ellagic and salicylic acids. This study aimed to exploit the potential of the WrbA scaffold as...

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Autores principales: Ratti, Alessandro, Fassi, Enrico M. A., Forlani, Fabio, Zangrossi, Maurizio, Mori, Matteo, Cappitelli, Francesca, Roda, Gabriella, Villa, Stefania, Villa, Federica, Grazioso, Giovanni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10451263/
https://www.ncbi.nlm.nih.gov/pubmed/37627607
http://dx.doi.org/10.3390/antiox12081612
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author Ratti, Alessandro
Fassi, Enrico M. A.
Forlani, Fabio
Zangrossi, Maurizio
Mori, Matteo
Cappitelli, Francesca
Roda, Gabriella
Villa, Stefania
Villa, Federica
Grazioso, Giovanni
author_facet Ratti, Alessandro
Fassi, Enrico M. A.
Forlani, Fabio
Zangrossi, Maurizio
Mori, Matteo
Cappitelli, Francesca
Roda, Gabriella
Villa, Stefania
Villa, Federica
Grazioso, Giovanni
author_sort Ratti, Alessandro
collection PubMed
description Biofilm-dwelling cells endure adverse conditions, including oxidative imbalances. The NADH:quinone oxidoreductase enzyme WrbA has a crucial role in the mechanism of action of antibiofilm molecules such as ellagic and salicylic acids. This study aimed to exploit the potential of the WrbA scaffold as a valuable target for identifying antibiofilm compounds at non-lethal concentrations. A three-dimensional computational model, based on the published WrbA structure, was used to screen natural compounds from a virtual library of 800,000 compounds. Fisetin, morin, purpurogallin, NZ028, and NZ034, along with the reference compound ellagic acid, were selected. The antibiofilm effect of the molecules was tested at non-lethal concentrations evaluating the cell-adhesion of wild-type and WrbA-deprived Escherichia coli strains through fluorochrome-based microplate assays. It was shown that, except for NZ028, all of the selected molecules exhibited notable antibiofilm effects. Purpurogallin and NZ034 showed excellent antibiofilm performances at the lowest concentration of 0.5 μM, in line with ellagic acid. The observed loss of activity and the level of reactive oxygen species in the mutant strain, along with the correlation with terms contributing to the ligand-binding free energy on WrbA, strongly indicates the WrbA-dependency of purpurogallin and NZ034. Overall, the molecular target WrbA was successfully employed to identify active compounds at non-lethal concentrations, thus revealing, for the first time, the antibiofilm efficacy of purpurogallin and NZ034.
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spelling pubmed-104512632023-08-26 Unlocking the Antibiofilm Potential of Natural Compounds by Targeting the NADH:quinone Oxidoreductase WrbA Ratti, Alessandro Fassi, Enrico M. A. Forlani, Fabio Zangrossi, Maurizio Mori, Matteo Cappitelli, Francesca Roda, Gabriella Villa, Stefania Villa, Federica Grazioso, Giovanni Antioxidants (Basel) Article Biofilm-dwelling cells endure adverse conditions, including oxidative imbalances. The NADH:quinone oxidoreductase enzyme WrbA has a crucial role in the mechanism of action of antibiofilm molecules such as ellagic and salicylic acids. This study aimed to exploit the potential of the WrbA scaffold as a valuable target for identifying antibiofilm compounds at non-lethal concentrations. A three-dimensional computational model, based on the published WrbA structure, was used to screen natural compounds from a virtual library of 800,000 compounds. Fisetin, morin, purpurogallin, NZ028, and NZ034, along with the reference compound ellagic acid, were selected. The antibiofilm effect of the molecules was tested at non-lethal concentrations evaluating the cell-adhesion of wild-type and WrbA-deprived Escherichia coli strains through fluorochrome-based microplate assays. It was shown that, except for NZ028, all of the selected molecules exhibited notable antibiofilm effects. Purpurogallin and NZ034 showed excellent antibiofilm performances at the lowest concentration of 0.5 μM, in line with ellagic acid. The observed loss of activity and the level of reactive oxygen species in the mutant strain, along with the correlation with terms contributing to the ligand-binding free energy on WrbA, strongly indicates the WrbA-dependency of purpurogallin and NZ034. Overall, the molecular target WrbA was successfully employed to identify active compounds at non-lethal concentrations, thus revealing, for the first time, the antibiofilm efficacy of purpurogallin and NZ034. MDPI 2023-08-14 /pmc/articles/PMC10451263/ /pubmed/37627607 http://dx.doi.org/10.3390/antiox12081612 Text en © 2023 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
Ratti, Alessandro
Fassi, Enrico M. A.
Forlani, Fabio
Zangrossi, Maurizio
Mori, Matteo
Cappitelli, Francesca
Roda, Gabriella
Villa, Stefania
Villa, Federica
Grazioso, Giovanni
Unlocking the Antibiofilm Potential of Natural Compounds by Targeting the NADH:quinone Oxidoreductase WrbA
title Unlocking the Antibiofilm Potential of Natural Compounds by Targeting the NADH:quinone Oxidoreductase WrbA
title_full Unlocking the Antibiofilm Potential of Natural Compounds by Targeting the NADH:quinone Oxidoreductase WrbA
title_fullStr Unlocking the Antibiofilm Potential of Natural Compounds by Targeting the NADH:quinone Oxidoreductase WrbA
title_full_unstemmed Unlocking the Antibiofilm Potential of Natural Compounds by Targeting the NADH:quinone Oxidoreductase WrbA
title_short Unlocking the Antibiofilm Potential of Natural Compounds by Targeting the NADH:quinone Oxidoreductase WrbA
title_sort unlocking the antibiofilm potential of natural compounds by targeting the nadh:quinone oxidoreductase wrba
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10451263/
https://www.ncbi.nlm.nih.gov/pubmed/37627607
http://dx.doi.org/10.3390/antiox12081612
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