Furvina inhibits the 3-oxo-C12-HSL-based quorum sensing system of Pseudomonas aeruginosa and QS-dependent phenotypes

Biofouling. 2017 Feb;33(2):156-168. doi: 10.1080/08927014.2017.1280732. Epub 2017 Jan 31.

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.

Keywords: Antimicrobial resistance; antivirulence; biofilm; furvina; quorum sensing inhibition.

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Furans / pharmacology*
  • Homoserine / analogs & derivatives*
  • Homoserine / metabolism
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation
  • Phenotype
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / physiology
  • Quorum Sensing / drug effects*
  • Vinyl Compounds / pharmacology*
  • Virulence Factors / metabolism

Substances

  • 2-bromo-5-(2-bromo-2-nitrovinyl)furan
  • Anti-Bacterial Agents
  • Furans
  • N-(3-oxododecanoyl)homoserine lactone
  • Vinyl Compounds
  • Virulence Factors
  • Homoserine
  • 4-Butyrolactone