2-(2-Methyl-2-nitrovinyl)furan but Not Furvina Interfere with <i>Staphylococcus aureus</i> Agr Quorum-Sensing System and Potentiate the Action of Fusidic Acid against Biofilms
Quorum sensing (QS) plays an essential role in the production of virulence factors, in biofilm formation and antimicrobial resistance. Consequently, inhibiting QS is being considered a promising target for antipathogenic/anti-virulence therapies. This study aims to screen 2-nitrovinylfuran derivativ...
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MDPI AG
2021-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/2/613 |
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| author | Diana Oliveira Anabela Borges Reinaldo Molina Ruiz Zenaida Rodríguez Negrín Simona Distinto Fernanda Borges Manuel Simões |
| author_facet | Diana Oliveira Anabela Borges Reinaldo Molina Ruiz Zenaida Rodríguez Negrín Simona Distinto Fernanda Borges Manuel Simões |
| author_sort | Diana Oliveira |
| collection | DOAJ |
| description | Quorum sensing (QS) plays an essential role in the production of virulence factors, in biofilm formation and antimicrobial resistance. Consequently, inhibiting QS is being considered a promising target for antipathogenic/anti-virulence therapies. This study aims to screen 2-nitrovinylfuran derivatives structurally related to Furvina (a broad-spectrum antibiotic already used for therapeutic purposes) for their effects on QS and in biofilm prevention/control. Furvina and four 2-nitrovinylfuran derivatives (compounds <b>1</b>–<b>4</b>) were tested to assess the ability to interfere with QS of <i>Staphylococcus aureus</i> using bioreporter strains (<i>S. aureus</i> ALC1742 and ALC1743). The activity of Furvina and the most promising quorum-sensing inhibitor (QSI) was evaluated in biofilm prevention and in biofilm control (combined with fusidic acid). The biofilms were further characterized in terms of biofilm mass, viability and membrane integrity. Compound <b>2</b> caused the most significant QS inhibition with reductions between 60% and 80%. Molecular docking simulations indicate that this compound interacts preferentially with the protein hydrophobic cleft in the LytTR domain of AgrA pocket. Metabolic inactivations of 40% for <i>S. aureus</i> ALC1742 and 20% for <i>S. aureus</i> ALC1743 were reached. A 24 h-old biofilm formed in the presence of the QSI increased the metabolic inactivation by fusidic acid to 80%, for both strains. The overall results highlight the effects of compound <b>2</b> as well as the potential of combining QSI with in-use antibiotics for the management of skin and soft tissues infections. |
| first_indexed | 2024-03-09T05:25:05Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T05:25:05Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3641f9b8b3ee4b6da7991e4c7448e7202023-12-03T12:36:56ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-0122261310.3390/ijms220206132-(2-Methyl-2-nitrovinyl)furan but Not Furvina Interfere with <i>Staphylococcus aureus</i> Agr Quorum-Sensing System and Potentiate the Action of Fusidic Acid against BiofilmsDiana Oliveira0Anabela Borges1Reinaldo Molina Ruiz2Zenaida Rodríguez Negrín3Simona Distinto4Fernanda Borges5Manuel Simões6LEPABE–Laboratory for Process Engineering, Environment, Biotechnology and Energy, Department of Chemical Engineering, Faculty of Engineering, University of Porto, 4200-465 Porto, PortugalLEPABE–Laboratory for Process Engineering, Environment, Biotechnology and Energy, Department of Chemical Engineering, Faculty of Engineering, University of Porto, 4200-465 Porto, PortugalCentro de Bioactivos Quimico, Universidad Central de las Villas, 54830 Santa Clara, CubaCentro de Bioactivos Quimico, Universidad Central de las Villas, 54830 Santa Clara, CubaDepartment of Life and Environmental Sciences, University of Cagliari, Via Ospedale 72, 09124 Cagliari, ItalyCIQUP—Research Center in Chemistry, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, PortugalLEPABE–Laboratory for Process Engineering, Environment, Biotechnology and Energy, Department of Chemical Engineering, Faculty of Engineering, University of Porto, 4200-465 Porto, PortugalQuorum sensing (QS) plays an essential role in the production of virulence factors, in biofilm formation and antimicrobial resistance. Consequently, inhibiting QS is being considered a promising target for antipathogenic/anti-virulence therapies. This study aims to screen 2-nitrovinylfuran derivatives structurally related to Furvina (a broad-spectrum antibiotic already used for therapeutic purposes) for their effects on QS and in biofilm prevention/control. Furvina and four 2-nitrovinylfuran derivatives (compounds <b>1</b>–<b>4</b>) were tested to assess the ability to interfere with QS of <i>Staphylococcus aureus</i> using bioreporter strains (<i>S. aureus</i> ALC1742 and ALC1743). The activity of Furvina and the most promising quorum-sensing inhibitor (QSI) was evaluated in biofilm prevention and in biofilm control (combined with fusidic acid). The biofilms were further characterized in terms of biofilm mass, viability and membrane integrity. Compound <b>2</b> caused the most significant QS inhibition with reductions between 60% and 80%. Molecular docking simulations indicate that this compound interacts preferentially with the protein hydrophobic cleft in the LytTR domain of AgrA pocket. Metabolic inactivations of 40% for <i>S. aureus</i> ALC1742 and 20% for <i>S. aureus</i> ALC1743 were reached. A 24 h-old biofilm formed in the presence of the QSI increased the metabolic inactivation by fusidic acid to 80%, for both strains. The overall results highlight the effects of compound <b>2</b> as well as the potential of combining QSI with in-use antibiotics for the management of skin and soft tissues infections.https://www.mdpi.com/1422-0067/22/2/613Furvina2-nitrovinylfuran derivatives<i>Staphylococcus aureus</i>quorum-sensing inhibitionbiofilmsantimicrobial combination |
| spellingShingle | Diana Oliveira Anabela Borges Reinaldo Molina Ruiz Zenaida Rodríguez Negrín Simona Distinto Fernanda Borges Manuel Simões 2-(2-Methyl-2-nitrovinyl)furan but Not Furvina Interfere with <i>Staphylococcus aureus</i> Agr Quorum-Sensing System and Potentiate the Action of Fusidic Acid against Biofilms International Journal of Molecular Sciences Furvina 2-nitrovinylfuran derivatives <i>Staphylococcus aureus</i> quorum-sensing inhibition biofilms antimicrobial combination |
| title | 2-(2-Methyl-2-nitrovinyl)furan but Not Furvina Interfere with <i>Staphylococcus aureus</i> Agr Quorum-Sensing System and Potentiate the Action of Fusidic Acid against Biofilms |
| title_full | 2-(2-Methyl-2-nitrovinyl)furan but Not Furvina Interfere with <i>Staphylococcus aureus</i> Agr Quorum-Sensing System and Potentiate the Action of Fusidic Acid against Biofilms |
| title_fullStr | 2-(2-Methyl-2-nitrovinyl)furan but Not Furvina Interfere with <i>Staphylococcus aureus</i> Agr Quorum-Sensing System and Potentiate the Action of Fusidic Acid against Biofilms |
| title_full_unstemmed | 2-(2-Methyl-2-nitrovinyl)furan but Not Furvina Interfere with <i>Staphylococcus aureus</i> Agr Quorum-Sensing System and Potentiate the Action of Fusidic Acid against Biofilms |
| title_short | 2-(2-Methyl-2-nitrovinyl)furan but Not Furvina Interfere with <i>Staphylococcus aureus</i> Agr Quorum-Sensing System and Potentiate the Action of Fusidic Acid against Biofilms |
| title_sort | 2 2 methyl 2 nitrovinyl furan but not furvina interfere with i staphylococcus aureus i agr quorum sensing system and potentiate the action of fusidic acid against biofilms |
| topic | Furvina 2-nitrovinylfuran derivatives <i>Staphylococcus aureus</i> quorum-sensing inhibition biofilms antimicrobial combination |
| url | https://www.mdpi.com/1422-0067/22/2/613 |
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