Chapter 15 : Regulation of Toxin Production in

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This chapter discusses our current understanding of gene regulation in , focusing on how toxin production is regulated, with a particular emphasis on the major toxins, toxin A and toxin B. The onset of toxin synthesis is associated with entry into the stationary phase of growth. The precise growth phase signals involved in the initiation of toxin production remain unknown, even though nutrient signals have clearly been shown to have a profound effect on toxin production by . TcdA and TcdB are encoded by and , respectively, which are located in a region of the chromosome known as the pathogenicity locus (PaLoc). The TcdR protein has a helix-turn-helix DNA binding motif and has limited similarity to some clostridial transcriptional activator proteins, as well as to several families of eubacterial RNA polymerase sigma factors, which is consistent with the hypothesis that TcdR is a positive regulator of toxin production. The regulation of toxin production in is clearly complex and relies on a number of different regulatory systems. In species, activation of Spo0A occurs via a phosphorelay cascade that eventuates in the phosphorylation of Spo0A via Spo0F and Spo0B. SigH is an alternative sigma factor that is involved in the transition to stationary phase and sporulation. Recent breakthroughs in genetic manipulation technologies available for , together with refined animal infection models, will facilitate future studies and will further define the complex regulatory networks involved in toxin regulation.

Citation: Carter G, Mackin K, Rood J, Lyras D. 2013. Regulation of Toxin Production in , p 295-306. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch15
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Figure 1

Structure of the PaLoc and flanking regions. Filled arrows indicate open reading frames, with arrows showing the direction of transcription. Toxin genes are shown in blue, regulatory genes are in orange and green, is in yellow, and genes located outside the PaLoc are in grey. The sigma factor TcdR interacts with the core RNA polymerase protein, facilitating recognition of the , , and promoters by the TcdR-RNA polymerase complex and promoting transcription from these promoters. The anti-sigma factor TcdC negatively regulates transcription by interacting with TcdR. doi:10.1128/9781555818524.ch15f1

Citation: Carter G, Mackin K, Rood J, Lyras D. 2013. Regulation of Toxin Production in , p 295-306. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch15
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Figure 2

Activation of by CdtR. An unknown signal activates the putative CdtS sensor histidine kinase, which then leads to the phosphorylation (P) of the response regulator CdtR. Phosphorylated CdtR activates the transcription of the operon, which is part of the chromosomal CdtLoc, as shown. doi:10.1128/9781555818524.ch15f2

Citation: Carter G, Mackin K, Rood J, Lyras D. 2013. Regulation of Toxin Production in , p 295-306. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch15
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