title: Proline-dependent regulation of Clostridium difficile Stickland metabolism.
abstract: Clostridium difficile, a proteolytic Gram-positive anaerobe, has emerged as a significant nosocomial pathogen. Stickland fermentation reactions are thought to be important for growth of C. difficile and appear to influence toxin production. In Stickland reactions, pairs of amino acids donate and accept electrons, generating ATP and reducing power in the process. Reduction of the electron acceptors proline and glycine requires the d-proline reductase (PR) and the glycine reductase (GR) enzyme complexes, respectively. Addition of proline in the medium increases the level of PR protein but decreases the level of GR. We report the identification of PrdR, a protein that activates transcription of the PR-encoding genes in the presence of proline and negatively regulates the GR-encoding genes. The results suggest that PrdR is a central metabolism regulator that controls preferential utilization of proline and glycine to produce energy via the Stickland reactions.
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bouillaut
authors.forename: William T
authors.initials: WT
authors.lastname: Self
authors.forename: Abraham L
authors.initials: AL
authors.lastname: Sonenshein
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D016360:Clostridioides difficile / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli; D005285:Fermentation; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D005998:Glycine / Q000378:metabolism; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D009876:Operon; D010957:Plasmids / Q000235:genetics; D011392:Proline / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D009097:Multienzyme Complexes; D011392:Proline; C022452:D-proline reductase (dithiol); D000594:Amino Acid Oxidoreductases; C020815:glycine reductase; D005998:Glycine