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公开(公告)号：US12011466B2
公开(公告)日：2024-06-18
申请号：US17625220
申请日：2020-07-07
申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) , UNIVERSITÉ TOULOUSE III—PAUL SABATIER , ECOLE NATIONALE VÉTÉRINAIRE DE TOULOUSE , INSTITUT NATIONAL DE RECHERCHE POUR L'AGRICULTURE, L'ALIMENTATION ET L'ENVIRONNEMENT (INRAE) , CENTRE HOSPITALIER UNIVERSITAIRE DE TOULOUSE
IPC分类号： A61K35/741 , A61P1/00 , C12N1/20 , C12N9/48 , C12R1/19
CPC分类号： A61K35/741 , A61P1/00 , C12N1/205 , C12N9/485 , C12R2001/19
摘要： The invention relates to the field of modified Escherichia coli strain 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 the Escherichia coli strain 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 an Escherichia coli strain 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.
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公开(公告)号：US20220265731A1
公开(公告)日：2022-08-25
申请号：US17625220
申请日：2020-07-07
申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) , UNIVERSITÉ TOULOUSE III - PAUL SABATIER , ECOLE NATIONALE VÉTÉRINAIRE DE TOULOUSE , INSTITUT NATIONAL DE RECHERCHE POUR L'AGRICULTURE, L'ALIMENTATION ET L'ENVIRONNEMENT , CENTRE HOSPITALIER UNIVERSITAIRE DE TOULOUSE
IPC分类号： A61K35/741 , C12N9/48 , A61P1/00 , C12N1/20
摘要： The invention relates to the field of modified Escherichia coli strain Nissle 1917 (EcN) and its use for treating gastro-in-testinal disorders. The invention is based on the study of the mechanisms implicated in the probiotic properties of the Escherichia coli strain 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 an Escherichia coli strain 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.
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公开(公告)号：US11912645B2
公开(公告)日：2024-02-27
申请号：US16607772
申请日：2018-04-27
申请人： INSERM (Institut National de la Santé et de la Recherche Médicale) , Université Paul Sabatier Toulouse III , Centre National de la Recherche Scientifique (CNRS) , Centre Hospitalier Universitaire de Toulouse , Ecole Nationale Vétérinaire de Toulouse
发明人： Nicolas Cenac , Justine Bertrand-Michel , Teresa Perez-Berezo , Thierry Durand , Jean-Marie Galano , Julien Pujo , Eric Oswald , Patricia Martin , Pauline Le Faouder , Alexandre Guy
IPC分类号： C07C233/47 , A61P29/00
CPC分类号： C07C233/47 , A61P29/00
摘要： 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 probiotic Escherichia coli strain 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.
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公开(公告)号：US10709776B2
公开(公告)日：2020-07-14
申请号：US15302279
申请日：2015-04-07
申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) , CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) , INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE (INRA) , UNIVERSITÉ PAUL SABATIER TOULOUSE III , CENTRE HOSPITALIER UNIVERSITAIRE DE TOULOUSE
发明人： Eric Oswald , Patricia Martin , Kazunori Murase
IPC分类号： A61K39/108 , C12N1/20 , A61K39/00 , C12N1/06 , C07K14/245 , C12N1/02 , C12Q1/18
摘要： 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.
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