Institut National De La Sante Et De La Recherche Medicale

Université Paul Sabatier (toulouse Iii)

Institut National De Recherche Pour L'agriculture, L'alimentation Et L'environnement

Centre Hospitalier Universitaire De Toulouse

Centre National De La Recherche Scientifique

Ecole Nationale Veterinaire De Toulouse

Universitè De Montpellier

Ecole Nationale Superieure De Chimie De Montpellier

Centre National De La Recherche Scientifique-cnrs

Inserm (institut National De La Sante Et De La Recherche Medicale)

Patricia Martin

Eric Oswald

Thierry Durand

Julien Pujo

Alexandre Guy

Teresa Perez-Berezo

Priscilla Branchu

Pauline Le Faouder

Jean-Marie Galano

Jean-Philippe Nougayrede

Justine Bertrand-Michel

Nicolas Cenac

Kazunori Murase

Clémence Massip

The invention relates to the field of modifiedstrain Nissle 1917 (EcN) and its use for treating gastro-intestinal disorders. The invention is based on the study of the mechanisms implicated in the probiotic properties of thestrain Nissle 1917 (EcN). This study has allowed the inventors to decouple the probiotic activity of EcN from its genotoxic activity by demonstrating that EcN ClbP protein, the enzyme that activates the genotoxin colibactin, is also required for the siderophore-microcins activity of probiotic EcN, but interestingly, not its enzymatic domain that cleaves precolibactin to form active colibactin. Furthermore, inventors demonstrate in an in vivo animal model infected by a bacterial pathogen that administration of an EcN modified strain with clbP gene encoding ClbP protein inactive for the peptidase domain, is non-genotoxic (do not produce colibactin) but keeps the bacterial antagonist activity, and reduces colonization and virulence of the pathogen by maintaining the siderophore-microcin production. Thus this study opens the way to safe use of EcN and accordingly the present invention provides anstrain Nissle 1917 (EcN) bacterium carrying a gene encoding ClbP protein which is inactive for the peptidase domain, and its use as a drug and more particularly for use in the treatment of gastro-intestinal disease.

Modifiedstrain Nissle and treatment of gastrointestinal disorder

The invention is based on the discovery of a new bacterial compound with analgesic properties which could be used as a new tool for the treatment of pain disorders such as visceral pain. Studying the mechanisms implicated in analgesic properties of the probioticstrain Nissle 1917 (EcN), inventors characterized, the amino fatty acids produced by EcN, which display the Ecn analgesic properties. One of these compounds inhibits the hypersensitivity to colorectal distension induced by capsaicin, which is a very powerful nociceptive compound and acts via the GABA B receptor. Furthermore, inventors demonstrate that this compound is able to cross the cellular epithelial barrier (such as the intestinal epithelium). Thus, the invention relates to a lipopetide compound, derived from gamma-aminobutyric acid. The invention also relates to a lipopeptide compound according to the invention for the treatment of treating pain disorder, such as somatic pain and visceral pain.

Lipopeptide compounds for the treatment of pain disorders

The present invention relates to ex vivo method for producing outer membrane vesicles (OMVs) by expression or overexpression of the hemolysin F gene (hlyF) in gram-negative bacterium.

Method for producing outer membrane vesicles

Growing community of inventors

Toulouse, France

Patricia Martin