Identification of an analgesic lipopeptide produced by the probiotic Escherichia coli strain Nissle 1917

Teresa Pérez-Berezo, Julien Pujo, Patricia Martin, Pauline Faouder, Jean-Marie Galano, Alexandre Guy, Claude Knauf, Jean Claude Tabet, Sophie Tronnet, Frederick Barreau, Maud Heuillet, Gilles Dietrich, Justine Bertrand-Michel, Thierry Durand, Eric Oswald and Nicolas Cenac ()
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Teresa Pérez-Berezo: IRSD, Université de Toulouse, INSERM, INRA, INP-ENVT, Université de Toulouse 3 Paul Sabatier
Julien Pujo: IRSD, Université de Toulouse, INSERM, INRA, INP-ENVT, Université de Toulouse 3 Paul Sabatier
Patricia Martin: IRSD, Université de Toulouse, INSERM, INRA, INP-ENVT, Université de Toulouse 3 Paul Sabatier
Pauline Faouder: MetaToulLipidomics Facility, INSERM UMR1048
Jean-Marie Galano: Institut des Biomolécules Max Mousseron IBMM, UMR 5247 CNRS, Université de Montpellier-ENSCM
Alexandre Guy: Institut des Biomolécules Max Mousseron IBMM, UMR 5247 CNRS, Université de Montpellier-ENSCM
Claude Knauf: IRSD, Université de Toulouse, INSERM, INRA, INP-ENVT, Université de Toulouse 3 Paul Sabatier
Jean Claude Tabet: Sorbonne Université, UPMC Univ Paris 06, CNRS, Institut Parisien de Chimie Moléculaire (IPCM)
Sophie Tronnet: IRSD, Université de Toulouse, INSERM, INRA, INP-ENVT, Université de Toulouse 3 Paul Sabatier
Frederick Barreau: IRSD, Université de Toulouse, INSERM, INRA, INP-ENVT, Université de Toulouse 3 Paul Sabatier
Maud Heuillet: LISBP, Université de Toulouse, CNRS, INRA, INSA
Gilles Dietrich: IRSD, Université de Toulouse, INSERM, INRA, INP-ENVT, Université de Toulouse 3 Paul Sabatier
Justine Bertrand-Michel: MetaToulLipidomics Facility, INSERM UMR1048
Thierry Durand: Institut des Biomolécules Max Mousseron IBMM, UMR 5247 CNRS, Université de Montpellier-ENSCM
Eric Oswald: IRSD, Université de Toulouse, INSERM, INRA, INP-ENVT, Université de Toulouse 3 Paul Sabatier
Nicolas Cenac: IRSD, Université de Toulouse, INSERM, INRA, INP-ENVT, Université de Toulouse 3 Paul Sabatier

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: Abstract Administration of the probiotic Escherichia coli strain Nissle 1917 (EcN) decreases visceral pain associated with irritable bowel syndrome. Mutation of clbA, a gene involved in the biosynthesis of secondary metabolites, including colibactin, was previously shown to abrogate EcN probiotic activity. Here, we show that EcN, but not an isogenic clbA mutant, produces an analgesic lipopeptide. We characterize lipoamino acids and lipopeptides produced by EcN but not by the mutant by online liquid chromatography mass spectrometry. One of these lipopeptides, C12AsnGABAOH, is able to cross the epithelial barrier and to inhibit calcium flux induced by nociceptor activation in sensory neurons via the GABAB receptor. C12AsnGABAOH inhibits visceral hypersensitivity induced by nociceptor activation in mice. Thus, EcN produces a visceral analgesic, which could be the basis for the development of new visceral pain therapies.

Date: 2017
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DOI: 10.1038/s41467-017-01403-9

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