Can the quorum sensing inhibitor resveratrol function as an aminoglycoside antibiotic accelerant against Pseudomonas aeruginosa?

Pseudomonas aeruginosa infection is a serious disease in cystic fibrosis patients and is difficult to treat owing to biofilm persistence and emerging multidrug resistance. Considering the essential role of quorum sensing (QS) in P. aeruginosa infections, the enhanced effects between the quorum sensing inhibitor (QSI) resveratrol and several antibiotics against P. aeruginosa PAO1 were investigated. Crystal violet staining assay revealed that biofilms of P. aeruginosa PAO1 grown in the presence of resveratrol were more susceptible to aminoglycoside antibiotics. Scanning electron and fluorescence microscopy showed architectural disruption of the biofilms when treated with resveratrol and aminoglycoside antibiotics. Furthermore, quantitative reverse transcription PCR (qRT-PCR) analysis demonstrated that expression of lasI and rhlI, two genes encoding enzymes that synthesise signal molecules in QS systems, were inhibited in the P. aeruginosa PAO1 biofilms by resveratrol. These results indicate that the QSI resveratrol can significantly enhance the effects of aminoglycoside antibiotics (e.g. tobramycin, gentamicin, amikacin and netilmicin) on P. aeruginosa PAO1 biofilms. These findings suggest that resveratrol is a potential accelerant in the treatment of P. aeruginosa biofilms and can restore or enhance the efficacy of aminoglycoside antibiotics.

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

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.

The quorum-sensing inhibiting effects of stilbenoids and their potential structure-activity relationship.

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.

Transcriptome analysis of the biofilm formed by methicillin-susceptible Staphylococcus aureus.

Biofilm formation is regarded as one of the major determinants in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) as pathogens of medical device-related infection. However, methicillin-susceptible S. aureus (MSSA) can also form biofilm in vitro and such biofilms are resistant to vancomycin. Hence, researching the possible mechanisms of MSSA biofilm formation is urgent and necessary. Here, we used S. aureus ATCC25923 as the model strain, and studied gene expression profiles in biofilms after the treatment of ursolic acid and resveratrol using RNA-seq technology. The results showed that only ursolic acid could inhibit biofilm formation, which differed from their applied on the multiple clinical drugs resistant MRSA biofilm. RNA-seq data was validated by examining the expression of six genes involved in biofilm formation by qRT-PCR. These data analysis indicated that the mechanism of the MSSA biofilm formation was different from that of the MRSA, due to absence of accessory gene regulator (agr) function. These findings suggest that biofilms of S. aureus with agr dysfunction may be more resistant than those with agr function. Therefore, the infection from clinical MSSA may be recalcitrant once forming biofilm. Further study is necessary to uncover the mechanisms of biofilm formation in other clinical S. aureus.