Cholesterol specificity of some heptameric beta-barrel pore-forming bacterial toxins: structural and functional aspects

Abstract

Apart from the thiol-specific/cholesterol-dependent cytolysin family of toxins (see Chapter 20) there are a number of other unrelated bacterial toxins that also have an affinity for plasma membrane cholesterol. Emphasis is given here on the Vibrio cholerae cytolysin (VCC) and the cytolysins from related Vibrio species. The inhibition of the cytolytic activity of these toxins by prior incubation with extracellular cholesterol or low density lipoprotein emerges as a unifying feature, as does plasma membrane cholesterol depletion. Incubation of VCC with cholesterol produces a heptameric oligomer, which is not equivalent to the pre-pore since it is unable to penetrate the plasma membrane. In structural terms, the precise sequence of VCC monomer binding to membrane, oligomer formation and pore insertion through the bilayer has yet to be fully defined. Several other bacterial toxins have a dependency for cholesterol, although the available data is limited in most cases.