REGULATED TRANSCRIPTION OF CLOSTRIDIUM-DIFFICILE TOXIN GENES

The Clostridium difficile toxA and toxB genes, encoding cytotoxic and enterotoxic proteins responsible for antibiotic-associated colitis and pseudomembranous colitis, were shown to be transcribed bath from gene -specific promoters and from promoters of upstream genes. However, the gene-specific transcripts represented the majority of fox gene mRNAs. The 5' ends of these mRNAs were shown to correspond to DNA sequences that had promoter activity when fused to the Escherichia coli beta-glu curonidase (gusA) gene and introduced into C. perfringens. The appeara nce of tox mRNA in C. difficile was repressed during exponential growt h phase but increased substantially as cells entered stationary phase. When glucose or other rapidly metabolizable sugars were present in th e medium, the stationary phase-associated induction was inhibited, ind icating that the toxin genes are subject to a form of catabolite repre ssion. This glucose effect was general to many toxinogenic strains hav ing varying levels of toxin production.