title: Furvina inhibits the 3-oxo-C12-HSL-based quorum sensing system of Pseudomonas aeruginosa and QS-dependent phenotypes.
abstract: Disruption of cell-cell communication or quorum sensing (QS) is considered a stimulating approach for reducing bacterial pathogenicity and resistance. Although several QS inhibitors (QSIs) have been discovered so far their clinical use remains distant. This problem can be circumvented by searching for QSI among drugs already approved for the treatment of different diseases. In this context, antibiotics have earned special attention. Whereas at high concentrations antibiotics exert a killing effect, at lower concentrations they may act as signaling molecules and as such can modulate gene expression. In this study, the antibiotic furvina was shown to be able to cause inhibition of the 3-oxo-C12-HSL-dependent QS system of Pseudomonas aeruginosa. Furvina interacts with the LasI/LasR system. The data were validated by modeling studies. Furvina can also reduce biofilm formation and decrease the production of QS-controlled virulence factors.
authors.affiliation: a LEPABE, Department of Chemical Engineering, Faculty of Engineering , University of Porto , Porto , Portugal.|b CIQ-UP, Department of Chemistry and Biochemistry, Faculty of Sciences , University of Porto , Porto , Portugal.|c CECAV-Veterinary and Animal Science Research Center, Department of Veterinary Science , University of Trás-os-Montes e Alto Douro , Vila Real , Portugal.
authors.forename: Anabela
authors.initials: A
authors.lastname: Borges
authors.affiliation: a LEPABE, Department of Chemical Engineering, Faculty of Engineering , University of Porto , Porto , Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Sousa
authors.affiliation: b CIQ-UP, Department of Chemistry and Biochemistry, Faculty of Sciences , University of Porto , Porto , Portugal.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gaspar
authors.affiliation: d Department of Biomedical Informatics , Columbia University , New York , USA.|e Department of Organic Chemistry, Faculty of Pharmacy , University of Santiago de Compostela , Santiago de Compostela , Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Vilar
authors.affiliation: b CIQ-UP, Department of Chemistry and Biochemistry, Faculty of Sciences , University of Porto , Porto , Portugal.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Borges
authors.affiliation: a LEPABE, Department of Chemical Engineering, Faculty of Engineering , University of Porto , Porto , Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Simões
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D005663:Furans / Q000494:pharmacology*; D006714:Homoserine / Q000031:analogs & derivatives* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D010641:Phenotype; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology; D053038:Quorum Sensing / Q000187:drug effects*; D014753:Vinyl Compounds / Q000494:pharmacology*; D037521:Virulence Factors / Q000378:metabolism
chemical_list: C577632:2-bromo-5-(2-bromo-2-nitrovinyl)furan; D000900:Anti-Bacterial Agents; D005663:Furans; C109860:N-(3-oxododecanoyl)homoserine lactone; D014753:Vinyl Compounds; D037521:Virulence Factors; D006714:Homoserine; D015107:4-Butyrolactone
keywords: Antimicrobial resistance; antivirulence; biofilm; furvina; quorum sensing inhibition