RESUMEN
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.
Asunto(s)
Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Regulación Bacteriana de la Expresión Génica , Pseudomonas aeruginosa/efectos de los fármacos , Percepción de Quorum/efectos de los fármacos , Estilbenos/farmacología , Antibacterianos/aislamiento & purificación , Ciclo del Ácido Cítrico/efectos de los fármacos , Glucólisis/efectos de los fármacos , Redes y Vías Metabólicas/efectos de los fármacos , Redes y Vías Metabólicas/genética , Metabolómica , Resonancia Magnética Nuclear Biomolecular , Estrés Oxidativo , Extractos Vegetales/química , Biosíntesis de Proteínas/efectos de los fármacos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Piocianina/antagonistas & inhibidores , Piocianina/biosíntesis , Resveratrol , Smilax/química , Estilbenos/aislamiento & purificación , Factores de Virulencia/antagonistas & inhibidores , Factores de Virulencia/biosíntesisRESUMEN
Stilbenoids, known an important phytoalexins in plants, were renowned for their beneficial effects on cardiovascular, neurological and hepatic systems. In the present study, quorum sensing inhibition activity of ten stilbenoids were tested using Chromobacterium violaceum CV026 as the bio-indicator strain and the structure-activity relationship was also investigated. Among them, resveratrol (1), piceatannol (2) and oxyresveratrol (3) showed potential anti-QS activities. At the sub-MIC concentrations, 1-3 demonstrated a statistically significant reduction of violacein in C. violaceum CV026 in a concentration dependent manner. Furthermore, the effects of 1-3 on QS regulated virulence factors in Pseudomonas aeruginosa PAO1 were also evaluated. Our results showed that the stilbenoids 1-3 can markedly decreased the production of pyocyanin and swarming motility of P. aeruginosa PAO1. Further transcriptome analyses showed that 1-3 suppressed the expression of QS-induced genes: lasR, lasI, rhlR and rhlI.