Proline-dependent regulation of Clostridium difficile Stickland metabolism

J Bacteriol. 2013 Feb;195(4):844-54. doi: 10.1128/JB.01492-12. Epub 2012 Dec 7.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Oxidoreductases / genetics
  • Amino Acid Oxidoreductases / metabolism
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Clostridioides difficile / genetics
  • Clostridioides difficile / metabolism*
  • Escherichia coli
  • Fermentation
  • Gene Expression Regulation, Bacterial / physiology*
  • Gene Expression Regulation, Enzymologic / physiology
  • Glycine / metabolism
  • Molecular Structure
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism
  • Operon
  • Plasmids / genetics
  • Proline / chemistry
  • Proline / metabolism*

Substances

  • Bacterial Proteins
  • Multienzyme Complexes
  • Proline
  • D-proline reductase (dithiol)
  • Amino Acid Oxidoreductases
  • glycine reductase
  • Glycine