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

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APPLIED MICROBIAL AND CELL PHYSIOLOGY

1-(4-Amino-2-hydroxyphenyl)ethanone from Phomopsis liquidambari showed quorum sensing inhibitory activity against Pseudomonas aeruginosa Jin-Wei Zhou 1 & Ai-Qun Jia 2

&

Huan Jiang 3 & Pei-Li Li 3 & Hong Chen 4 & Xiao-Juan Tan 5 & En-Qi Liu 1

Received: 20 July 2020 / Revised: 2 November 2020 / Accepted: 9 November 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract 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. Keywords 1-(4-Amino-2-hydroxyphenyl)ethanone . Pseudomonas aeruginosa . Quorum sensing . Metabolomics . Virulence

Introduction Pseudomonas aeruginosa is a notorious opportunistic pathogen that often infects immune-compromised patients and individuals with cystic fibrosis (Lee and Zhang 2015). The abuse of antibiotics has aggravated the worldwide * Ai-Qun Jia [email protected] * Xiao-Juan Tan [email protected] * En-Qi Liu [email protected] 1

School of Food and Biology Engineering, Xuzhou University of Technology, Xuzhou 221018, China

incidence of multidrug-resistant P. aeruginosa and renders current antibiotic treatment invalid in many cases. Therefore, it is urgent to develop novel alternative therapeutic measures that target nonessential pathways in bacteria involved in pathogenesis without creating survival pressure as antibiotics. 2

School of Life and Pharmaceutical Sciences, State Key Laboratory of Marine Resource Utilization in South China Sea, Hainan University, Haikou 570228, China

3

School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, China

4

Luoyang Key Laboratory of Organic Functional Molecules, College of Food and Drug, Luoyang Normal University, Luoyang 471934, China

5

Anhui Pro