Three-Component Regulatory System Controlling Virulence in Vibrio cholerae

Studies of virulence and its regulation in Vibrio cholerae 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 V. cholerae. 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 V. cholerae 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.