Titre :

Role of the global regulator Rex in control of NAD+‐regeneration inClostridioides (Clostridium) difficile

Auteur(s) :

Bouillaut, Laurent [Auteur]
Dubois, Thomas [Auteur]
Université Paris Diderot - Paris 7 [UPD7]
Pathogénèse des Bactéries Anaérobies / Pathogenesis of Bacterial Anaerobes [PBA (U-Pasteur_6)]
Francis, Michael B. [Auteur]
Daou, Nadine [Auteur]
Monot, Marc [Auteur]
Sorg, Joseph A. [Auteur]
Sonenshein, Abraham L. [Auteur]
Dupuy, Bruno [Auteur]

Titre de la revue :

Molecular Microbiology

Nom court de la revue :

Mol Microbiol

Numéro :

111

Pagination :

1671-1688

Éditeur :

Wiley

Date de publication :

2019-04-02

Mot(s)-clé(s) en anglais :

virulence
metabolism
amino acids
toxin production
enzymic reduction
proline reductase
anaerobes genus clostridium
repressor

Discipline(s) HAL :

Sciences du Vivant [q-bio]/Ingénierie des aliments

Résumé en anglais : [en]

For the human pathogen Clostridioides (also known as Clostridium) difficile, the ability to adapt to nutrient availability is critical for its proliferation and production of toxins during infection. Synthesis of the toxins ...
Lire la suite >For the human pathogen Clostridioides (also known as Clostridium) difficile, the ability to adapt to nutrient availability is critical for its proliferation and production of toxins during infection. Synthesis of the toxins is regulated by the availability of certain carbon sources, fermentation products and amino acids (e.g. proline, cysteine, isoleucine, leucine and valine). The effect of proline is attributable at least in part to its role as an inducer and substrate of D‐proline reductase (PR), a Stickland reaction that regenerates NAD+ from NADH. Many Clostridium spp. use Stickland metabolism (co‐fermentation of pairs of amino acids) to generate ATP and NAD+. Synthesis of PR is activated by PrdR, a proline‐responsive regulatory protein. Here we report that PrdR, in the presence of proline, represses other NAD+‐generating pathways, such as the glycine reductase and succinate‐acetyl CoA utilization pathways leading to butyrate production, but does so indirectly by affecting the activity of Rex, a global redox‐sensing regulator that responds to the NAD+/NADH ratio. Our results indicate that PR activity is the favored mechanism for NAD+ regeneration and that both Rex and PrdR influence toxin production. Using the hamster model of C. difficile infection, we revealed the importance of PrdR‐regulated Stickland metabolism in the virulence of C. difficile.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
CNRS
INRA
ENSCL

Collections :

• Unité Matériaux et Transformations (UMET) - UMR 8207

Équipe(s) de recherche :

Processus aux Interfaces et Hygiène des Matériaux (PIHM)

Date de dépôt :

2020-12-14T16:05:05Z