Title :

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

Author(s) :

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

Journal title :

Molecular Microbiology

Abbreviated title :

Mol Microbiol

Volume number :

111

Pages :

1671-1688

Publisher :

Wiley

Publication date :

2019-04-02

English keyword(s) :

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

HAL domain(s) :

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

English abstract : [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 ...
Show more >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.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CNRS
INRA
ENSCL

Collections :

• Unité Matériaux et Transformations (UMET) - UMR 8207

Research team(s) :

Processus aux Interfaces et Hygiène des Matériaux (PIHM)

Submission date :

2020-12-14T16:05:05Z