BotR/A and TetR are alternative RNA polymerase sigma factors controlling the expression of the neurotoxin and associated protein genes in Clostridium botulinum type A and Clostridium tetani

Mol Microbiol. 2005 Jan;55(1):235-49. doi: 10.1111/j.1365-2958.2004.04377.x.


Clostridium botulinum and Clostridium tetani, respectively, produce potent toxins, botulinum neurotoxin (BoNT) and tetanus neurotoxin (TeTx), which are responsible for severe diseases, botulism and tetanus. Neurotoxin synthesis is a regulated process in Clostridium. The genes botR/A in C. botulinum A and tetR in C. tetani positively regulate expression of BoNT/A and associated non-toxic proteins (ANTPs), as well as TeTx respectively. The botR/A gene lies in close vicinity of the two operons which contain bont/A and antps genes in C. botulinum A, and tetR immediately precedes the tetX gene in C. tetani. We show that BotR/A and TetR function as specific alternative sigma factors rather than positive regulators based on the following results: (i) BotR/A and TetR associated with target DNAs only in the presence of the RNA polymerase core enzyme (Core), (ii) BotR/A and TetR directly bound with the core enzyme, (iii) BotR/A-Core recognized -35 and -10 regions of ntnh-bont/A promoter and (iv) BotR/A and TetR triggered in vitro transcription from the target promoters. In C. botulinum A, bont/A and antps genes are transcribed as bi- and tricistronic operons controlled by BotR/A. BotR/A and TetR are seemingly related to a new subgroup of the sigma70 family that includes TcdR and UviA, which, respectively, regulate production of toxins A and B in C. difficile and bacteriocin in C. perfringens. Sequences of -35 region are highly conserved in the promoter of target toxin genes in C. botulinum, C. tetani, C. difficile and C. perfringens. Overall, a common regulation mechanism probably controls toxin gene expression in these four toxigenic clostridial species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / physiology*
  • Base Sequence
  • Botulinum Toxins / genetics*
  • Clostridium botulinum / genetics
  • Clostridium botulinum / physiology*
  • Clostridium tetani / genetics
  • Clostridium tetani / physiology*
  • DNA, Bacterial
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • DNA-Directed RNA Polymerases / genetics
  • DNA-Directed RNA Polymerases / metabolism
  • DNA-Directed RNA Polymerases / physiology
  • Gene Expression Regulation, Bacterial*
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Protein Binding
  • Sigma Factor / genetics
  • Sigma Factor / physiology*
  • Tetanus Toxin / genetics*
  • Trans-Activators / genetics
  • Trans-Activators / physiology*


  • Bacterial Proteins
  • BotR protein, Clostridium botulinum
  • DNA, Bacterial
  • DNA-Binding Proteins
  • Sigma Factor
  • TetR protein, Clostridium tetani
  • Tetanus Toxin
  • Trans-Activators
  • RNA polymerase sigma 70
  • DNA-Directed RNA Polymerases
  • Botulinum Toxins