Induction of toxins in Clostridium difficile is associated with dramatic changes of its metabolism

Microbiology (Reading). 2008 Nov;154(Pt 11):3430-3436. doi: 10.1099/mic.0.2008/019778-0.


Certain amino acids, and cysteine in particular, promptly blocked toxin expression in Clostridium difficile strain VPI 10463 when added to late-exponential-phase peptone-yeast cultures, i.e. prior to normal induction of toxins A and B. Glucose reduced toxin yields by 80-fold, but only when supplemented at inoculation. Forty upregulated C. difficile proteins were identified during maximum toxin expression, and most of these were enzymes involved in energy exchange, e.g. succinate, CO/folate and butyrate metabolism. Transcription of tcdA (toxin operon) and folD (CO/folate operon) was induced by 20- and 10-fold, respectively, and with strikingly similar kinetics between OD 0.8 and 1.2. The sigma factors tcdR and sigH were upregulated simultaneously with tcdA and folD (3.5-fold increase of mRNA level), whereas transcription of tcdC, codY, sigB and sigL showed little or no correlation with that of tcdA and folD. The results suggest a connection between toxin expression, alternative energy metabolism and initial sporulation events in C. difficile.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / genetics*
  • Bacterial Toxins / biosynthesis
  • Bacterial Toxins / genetics*
  • Clostridium difficile / genetics*
  • Clostridium difficile / metabolism*
  • Gene Expression Regulation, Bacterial
  • Glucose / metabolism
  • Transcription, Genetic
  • Transcriptional Activation*


  • Amino Acids
  • Bacterial Proteins
  • Bacterial Toxins
  • Glucose