Protoanemonin: a natural quorum sensing inhibitor that selectively activates iron starvation response

Authors

  • Roberto A. Bobadilla Fazzini,

    Corresponding author
    1. Systems and Synthetic Biology Group, HZI-Helmholtz-Zentrum für Infektionsforschung, Braunschweig, Germany
    2. Departamento de Prevencion de Riesgos y Medio Ambiente, Facultad de Ciencias de la Construccion y Ordenamiento Territorial, Universidad Tecnologica Metropolitana, Santiago de Chile, Chile
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  • Mette E. Skindersoe,

    1. Department for Microbiological Surveillance and Research, Statens Serum Institut, Oerestads Boulevard 5, DK-2300 Copenhagen S, Denmark
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  • Piotr Bielecki,

    1. Systems and Synthetic Biology Group, HZI-Helmholtz-Zentrum für Infektionsforschung, Braunschweig, Germany
    2. Department of Pathophysiology of Bacterial Biofilms, TWINCORE – Centre for Experimental and Clinical Infection Research, Hanover, Germany
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  • Jacek Puchałka,

    1. Systems and Synthetic Biology Group, HZI-Helmholtz-Zentrum für Infektionsforschung, Braunschweig, Germany
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  • Michael Givskov,

    1. Department for Microbiological Surveillance and Research, Statens Serum Institut, Oerestads Boulevard 5, DK-2300 Copenhagen S, Denmark
    2. Department of International Health, Immunology and Microbiology, Faculty of Health Sciences, University of Copenhagen Blegdamsvej 3B DK-2200 Copenhagen, Denmark
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  • Vitor A. P. Martins dos Santos

    1. Systems and Synthetic Biology Group, HZI-Helmholtz-Zentrum für Infektionsforschung, Braunschweig, Germany
    2. Laboratory of Systems and Synthetic Biology, Wageningen University, Dreijenplein 10, 6703 HB Wageningen, The Netherlands
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E-mail rbobadi@utem.cl; Tel. (+56) 2787 7300; Fax (+56) 2787 7321.

Summary

Many Gram-negative bacteria employ cell-to-cell communication mediated by N-acyl homoserine lactones (quorum sensing) to control expression of a wide range of genes including, but not limited to, genes encoding virulence factors. Outside the laboratory, the bacteria live in complex communities where signals may be perceived across species. We here present a newly found natural quorum sensing inhibitor, produced by the pseudomonads Pseudomonas sp. B13 and Pseudomonas reinekei MT1 as a blind end in the biodegradation of organochloride xenobiotics, which inhibits quorum sensing in P. aeruginosa in naturally occurring concentrations. This catabolite, 4-methylenebut-2-en-4-olide, also known as protoanemonin, has been reported to possess antibacterial properties, but seems to have dual functions. Using transcriptomics and proteomics, we found that protoanemonin significantly reduced expression of genes and secretion of proteins known to be under control of quorum sensing in P. aeruginosa. Moreover, we found activation of genes and gene products involved in iron starvation response. It is thus likely that inhibition of quorum sensing, as the production of antibiotics, is a phenomenon found in complex bacterial communities.

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