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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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