The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.
The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.
Patent No.:
Date of Patent:
Jun. 18, 2024
Filed:
Jul. 07, 2020
Inserm (Institut National DE LA Santé ET DE LA Recherche Médicale), Paris, FR;
Université Toulouse Iii—paul Sabatier, Toulouse, FR;
Ecole Nationale Vétérinaire DE Toulouse, Toulouse, FR;
Institut National DE Recherche Pour L'agriculture, L'alimentation ET L'environnement (Inrae), Paris, FR;
Centre Hospitalier Universitaire DE Toulouse, Toulouse, FR;
Eric Oswald, Toulouse, FR;
Jean-Philippe Nougayrede, Toulouse, FR;
Clémence Massip, Toulouse, FR;
Patricia Martin, Toulouse, FR;
Priscilla Branchu, Toulouse, FR;
INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE), Paris, FR;
UNIVERSITÉ PAUL SABATIER TOULOUSE III, Toulouse, FR;
ECOLE NATIONALE VÉTÉRINAIRE DE TOULOUSE, Toulouse, FR;
INSTITUT NATIONAL DE RECHERCHE POUR L'AGRICULTURE, L'ALIMENTATION ET L'ENVIRONNEMENT, Paris, FR;
CENTRE HOSPITALIER UNIVERSITAIRE DE TOULOUSE, Toulouse, FR;
Abstract
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.