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Chapter 22 : Three-Component Regulatory System Controlling Virulence in

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Abstract:

Studies of virulence and its regulation in have classically been devoted to understanding the mechanism and consequences of toxin production by this human pathogen. The cholera toxin is a very well-studied molecule and is the virulence factor of primary importance for pathogenicity of . More recent work identified several other gene products required for full virulence and showed that expression of these genes, which include those encoding a pilus colonization factor and an accessory colonization factor, is under coordinate control with cholera toxin expression. A large percentage of the inoculum is therefore probably killed in the first host environment encountered, which likely accounts for the high doses of organisms required to infect and for the fact that achlorhydric people (those with decreased stomach acidity) are more sensitive to cholera infection. Virulence factors coordinately expressed with cholera toxin include the toxin-coregulated pilus (TCP) and the accessory colonization factor (ACF). Several gene products are required for both TCP and ACF expression, and they are all regulated by the ToxR protein. Mutants were identified that expressed elevated alkaline phosphatase activity in the presence of ToxS but that did not simultaneously acquire ToxR activity. The output for ToxR activity in is virulence, but what is clear from investigations into this system so far is that along the way toward answering specific questions of virulence we are learning more about fundamental processes in molecular biology as well.

Citation: DiRita V. 1995. Three-Component Regulatory System Controlling Virulence in , p 351-365. In Hoch J, Silhavy T (ed), Two-Component Signal Transduction. ASM Press, Washington, DC. doi: 10.1128/9781555818319.ch22

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Outer Membrane Proteins
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Cholera Toxin
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Figures

Image of FIGURE 1
FIGURE 1

Model for the ToxR regulon in . The relative orientations of ToxR and ToxS with respect to the cytoplasmic membrane are indictated with N and C for the amino and carboxyl termini, respectively. ToxR* refers to the active form of ToxR, resulting from interaction with ToxS in the membrane. The putative carboxyl-terminal helix-loop-helix DNA binding domain of ToxT is indicated by h-l-h. See text for further details.

Citation: DiRita V. 1995. Three-Component Regulatory System Controlling Virulence in , p 351-365. In Hoch J, Silhavy T (ed), Two-Component Signal Transduction. ASM Press, Washington, DC. doi: 10.1128/9781555818319.ch22
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Image of FIGURE 2
FIGURE 2

Schematic representation of the ToxR mutants described in the text. The one-letter amino acid code is used, and the number represents the position in ToxR of each residue. The ToxS blind mutants are referred to with the wild-type residue followed by the mutant residue isolated in the screen described in the text. The OmpR-homologous residues that were studied by in vitro mutagenesis were changed to various different residues, as described in the text.

Citation: DiRita V. 1995. Three-Component Regulatory System Controlling Virulence in , p 351-365. In Hoch J, Silhavy T (ed), Two-Component Signal Transduction. ASM Press, Washington, DC. doi: 10.1128/9781555818319.ch22
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