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      Anti-Biofilm and Antivirulence Activities of Metabolites from Plectosphaerella cucumerina against Pseudomonas aeruginosa

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          Abstract

          This study reported the efficacy of the metabolites of Plectosphaerella cucumerina, one phyllosphere fungus from Orychophragmus violaceus, against Pseudomonas aeruginosa quorum sensing (QS) and QS-regulated biofilms. The minimum inhibitory concentration (MIC) of the ethyl acetate (EtOAc) extract from P. cucumerina against P. aeruginosa PAO1 was 1.25 mg mL −1. At sub-MIC concentrations, P. cucumerina extract (0.25–1 mg mL −1) not only inhibited biofilm formation but also disrupted preformed biofilms of P. aeruginosa PAO1 without affecting its growth. Fluorescence and scanning electron microscope (SEM) showed architectural disruption of the biofilms when treated with P. cucumerina metabolites. Further investigation demonstrated that metabolites in P. cucumerina attenuated the QS-dependent virulence factors. LC-MS/MS spectra coupled with experimentally standard samples suggested that patulin and emodin might act as the principal components possessing anti-biofilm and antivirulence activities. This is the first report of (1) the isolation of P. cucumerina from the phyllosphere of O. violaceus and (2) anti-biofilm, antivirulence, and biofilm disruption activities of this fungus. Thus, this study provides fascinating new pathways for screening antipathogenic agents.

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          Most cited references67

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          Bacterial quorum sensing: its role in virulence and possibilities for its control.

          Quorum sensing is a process of cell-cell communication that allows bacteria to share information about cell density and adjust gene expression accordingly. This process enables bacteria to express energetically expensive processes as a collective only when the impact of those processes on the environment or on a host will be maximized. Among the many traits controlled by quorum sensing is the expression of virulence factors by pathogenic bacteria. Here we review the quorum-sensing circuits of Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Vibrio cholerae. We outline these canonical quorum-sensing mechanisms and how each uniquely controls virulence factor production. Additionally, we examine recent efforts to inhibit quorum sensing in these pathogens with the goal of designing novel antimicrobial therapeutics.
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            Microbiology of the Phyllosphere

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              Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms.

              The bacterium Pseudomonas aeruginosa permanently colonizes cystic fibrosis lungs despite aggressive antibiotic treatment. This suggests that P. aeruginosa might exist as biofilms--structured communities of bacteria encased in a self-produced polymeric matrix--in the cystic fibrosis lung. Consistent with this hypothesis, microscopy of cystic fibrosis sputum shows that P. aeruginosa are in biofilm-like structures. P. aeruginosa uses extracellular quorum-sensing signals (extracellular chemical signals that cue cell-density-dependent gene expression) to coordinate biofilm formation. Here we found that cystic fibrosis sputum produces the two principal P. aeruginosa quorum-sensing signals; however, the relative abundance of these signals was opposite to that of the standard P. aeruginosa strain PAO1 in laboratory broth culture. When P. aeruginosa sputum isolates were grown in broth, some showed quorum-sensing signal ratios like those of the laboratory strain. When we grew these isolates and PAO1 in a laboratory biofilm model, the signal ratios were like those in cystic fibrosis sputum. Our data support the hypothesis that P. aeruginosa are in a biofilm in cystic fibrosis sputum. Moreover, quorum-sensing signal profiling of specific P. aeruginosa strains may serve as a biomarker in screens to identify agents that interfere with biofilm development.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                03 May 2017
                2017
                : 8
                : 769
                Affiliations
                [1] 1School of Environmental and Biological Engineering, Nanjing University of Science and Technology Nanjing, China
                [2] 2State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University Nanjing, China
                [3] 3State Key Laboratory of Marine Resource Utilization in South China Sea, Key Laboratory of Tropical Biological Resources of Ministry Education, Hainan University Haikou, China
                Author notes

                Edited by: Yuji Morita, Aichi Gakuin University, Japan

                Reviewed by: Mona I. Shaaban, Mansoura University, Egypt; Francesco Imperi, Sapienza University of Rome, Italy

                *Correspondence: Ai-Qun Jia aiqunj302@ 123456njust.edu.cn

                This article was submitted to Antimicrobials, Resistance and Chemotherapy, a section of the journal Frontiers in Microbiology

                †These authors have contributed equally to this work.

                Article
                10.3389/fmicb.2017.00769
                5413567
                28515715
                20a8eccf-0db0-4f0e-a861-3b68270c34e9
                Copyright © 2017 Zhou, Bi, Chen, Chen, Yang, Li, Fu and Jia.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 06 February 2017
                : 13 April 2017
                Page count
                Figures: 10, Tables: 1, Equations: 0, References: 76, Pages: 17, Words: 10884
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                plectosphaerella cucumerina,phyllosphere fungus,pseudomonas aeruginosa,biofilm,quorum sensing

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