1H NMR-Based Global Metabolic Studies of Pseudomonas aeruginosa upon Exposure of the Quorum Sensing Inhibitor Resveratrol

J Proteome Res. 2017 Feb 3;16(2):824-830. doi: 10.1021/acs.jproteome.6b00800. Epub 2017 Jan 26.

Abstract

Quorum sensing (QS) is a process of bacterial communication that has been a novel target for drug discovery. Pyocyanin quantification assay confirmed that resveratrol was an effective quorum sensing inhibitor (QSI) against Pseudomonas aeruginosa PAO1. In this study, the global metabolite changes of P. aeruginosa PAO1 exposed to QSI resveratrol were investigated by 1H NMR spectroscopy. A total of 40 metabolites containing amino acids, organic acid, organic amine, and energy storage compounds were identified. The changed metabolic profile indicated that resveratrol influenced pathways including oxidative stress, protein synthesis, and energy metabolism. Oxidative stress could upregulate the expression of genes related to QS in P. aeruginosa. It suggested that resveratrol could inhibit the QS systems in P. aeruginosa PAO1 by relieving oxidative stress due to its antioxidant activity. On the other hand, resveratrol could attenuate the pathogenicity of P. aeruginosa PAO1 by disturbing the TCA cycle so that anaerobic respiration could suppress the virulence because anaerobiosis could induce the loss of cytotoxicity regulated by QS in P. aeruginosa. These findings deepened our comprehending of the metabolic responses of P. aeruginosa PAO1 to resveratrol and pinpointed the possible underlying mechanism of resveratrol's inhibition effect on QS in P. aeruginosa PAO1.

Keywords: 1H NMR; Pseudomonas aeruginosa; metabolomics; quorum sensing; resveratrol.

MeSH terms

  • Anti-Bacterial Agents / isolation & purification
  • Anti-Bacterial Agents / pharmacology*
  • Biofilms / drug effects*
  • Citric Acid Cycle / drug effects
  • Gene Expression Regulation, Bacterial*
  • Glycolysis / drug effects
  • Metabolic Networks and Pathways / drug effects
  • Metabolic Networks and Pathways / genetics
  • Metabolomics
  • Nuclear Magnetic Resonance, Biomolecular
  • Oxidative Stress
  • Plant Extracts / chemistry
  • Protein Biosynthesis / drug effects
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / metabolism
  • Pyocyanine / antagonists & inhibitors
  • Pyocyanine / biosynthesis
  • Quorum Sensing / drug effects*
  • Resveratrol
  • Smilax / chemistry
  • Stilbenes / isolation & purification
  • Stilbenes / pharmacology*
  • Virulence Factors / antagonists & inhibitors
  • Virulence Factors / biosynthesis

Substances

  • Anti-Bacterial Agents
  • Plant Extracts
  • Stilbenes
  • Virulence Factors
  • Pyocyanine
  • Resveratrol