1-(4-Amino-2-hydroxyphenyl)ethanone from Phomopsis liquidambari showed quorum sensing inhibitory activity against Pseudomonas aeruginosa.

Phomopsis liquidambari S47 is an endophytic fungus isolated from the leaves of Punica granatum. Here, we are the first to report a quorum sensing (QS) inhibitor 1-(4-amino-2-hydroxyphenyl)ethanone (AHE) isolated and identified from the metabolites of P. liquidambari S47. Exposure to AHE at sub-MIC concentrations notably suppressed the secretion of acyl-homoserine lactones and virulence factors in Pseudomonas aeruginosa PAO1. To investigate the metabolic variations of P. aeruginosa PAO1 exposed to AHE, magnetic resonance imaging-based metabolomic analysis was performed. AHE treatment created a disturbance in the QS system by suppressing the expressions of QS-related genes. The disturbed QS system resulted in the inhibited activity of antioxidant enzymes and thus enhanced oxidative stress. The vegetable infection assay showed that the virulence of P. aeroginosa PAO1 was attenuated which could be due to the impacts to the amino acid and nucleotide metabolism by enhanced oxidative stress. These findings suggest that AHE has a potential to become an antivirulence "agent" to tackle P. aeruginosa infection. KEY POINTS: • AHE treatment inhibited AHL secretion and virulence factors production. • AHE treatment aggravated oxidative stress and disturbed metabolism. • AHE suppressed QS-related gene expressions and reduced virulence of P. aeruginosa.