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Chapter 12 : Regulation of Cholera Toxin Expression

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Abstract:

This chapter focuses on composition and molecular mechanism of control of ToxR regulon. Early studies of the in vitro production of cholera toxin defined certain conditions that increased overall levels of cholera toxin. Early work on the genetics of cholera toxin expression relied heavily on the use of chemical mutagenesis to produce mutants altered in toxinogenesis. The gene product is a 32-kDa integral inner membrane protein. The amino-terminal two-thirds of the protein is cytoplasmic, and the carboxyterminal one-third is periplasmic. ToxR-alkaline phosphatase fusions that replaced the majority of the periplasmic domain no longer responded to high osmolality. The cytoplasmic portion of ToxR contains a region of homology to OmpR. The function of this region has been characterized by taking advantage of this homology to indicate which amino acid residues may be important for function. Amino acid substitution of glutamic acid 51 with lysine resulted in inactive protein that was dominant over wild type. possesses an array of virulence factors that are highly regulated. Among the factors necessary for a successful infection are cholera toxin, the toxin-coregulated pilus, and other accessory colonization factors.

Citation: Ottemann K, Mekalanos J. 1994. Regulation of Cholera Toxin Expression, p 177-185. In Wachsmuth I, Blake P, Olsvik Ø (ed), and Cholera. ASM Press, Washington, DC. doi: 10.1128/9781555818364.ch12

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Cholera Toxin
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Outer Membrane Proteins
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Figures

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Figure 1

Model for regulation of the ToxR regulon. Expression of the toxRS operon is modulated by expression of the htpG gene in response to stress. The ToxR protein is depicted as a monomer that senses environmental signals and then undergoes a conformational change (here shown as dimerization) to become competent to activate transcription. This active ToxR is stabilized by the ToxS protein and activates transcription of both the ctxAB operon and the toxT gene. The ToxT protein then activates transcription of other virulence factors, including the tcp and ctxAB operons.

Citation: Ottemann K, Mekalanos J. 1994. Regulation of Cholera Toxin Expression, p 177-185. In Wachsmuth I, Blake P, Olsvik Ø (ed), and Cholera. ASM Press, Washington, DC. doi: 10.1128/9781555818364.ch12
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Image of Figure 2
Figure 2

Pictorial representation of fusion protein analysis of ToxR. Wild-type ToxR is shown at the top as a plain line, with the transmembrane region depicted as a box with TM above it. At the right is indicated the ability of ToxR to activate transcription in two different organisms: E. coli from a ctx::lacZ construct and V. cholerae from the ctx promoter. The different moieties that were fused to ToxR are depicted below, with their identities indicated in the legend at the bottom. The ability of each of these fusion proteins to activate transcription from the two constructs is indicated at the right.

Citation: Ottemann K, Mekalanos J. 1994. Regulation of Cholera Toxin Expression, p 177-185. In Wachsmuth I, Blake P, Olsvik Ø (ed), and Cholera. ASM Press, Washington, DC. doi: 10.1128/9781555818364.ch12
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