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.

Details

Title
Identification of an analgesic lipopeptide produced by the probiotic Escherichia coli strain Nissle 1917
Author
Pérez-Berezo, Teresa 1 ; Pujo, Julien 1 ; Martin, Patricia 2 ; Pauline Le Faouder 3 ; Galano, Jean-Marie 4 ; Guy, Alexandre 4 ; Knauf, Claude 1 ; Tabet, Jean Claude 5 ; Tronnet, Sophie 1 ; Barreau, Frederick 1 ; Heuillet, Maud 6 ; Dietrich, Gilles 1 ; Bertrand-Michel, Justine 3 ; Durand, Thierry 4 ; Oswald, Eric 2 ; Cenac, Nicolas 1 

 IRSD, Université de Toulouse, INSERM, INRA, INP-ENVT, Université de Toulouse 3 Paul Sabatier, Toulouse, France 
 IRSD, Université de Toulouse, INSERM, INRA, INP-ENVT, Université de Toulouse 3 Paul Sabatier, Toulouse, France; CHU Toulouse, Hôpital Purpan, Service de bactériologie-hygiène, Toulouse, France 
 MetaToulLipidomics Facility, INSERM UMR1048, Toulouse, France 
 Institut des Biomolécules Max Mousseron IBMM, UMR 5247 CNRS, Université de Montpellier-ENSCM, Montpellier, France 
 Sorbonne Université, UPMC Univ Paris 06, CNRS, Institut Parisien de Chimie Moléculaire (IPCM), Paris, France 
 LISBP, Université de Toulouse, CNRS, INRA, INSA, Toulouse, France 
Pages
1-12
Publication year
2017
Publication date
Nov 2017
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1960493581
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.