27 - Structural relationships between small β-pore-forming toxins from Clostridium perfringens

Abstract

Many pathogenic bacteria produce pore-forming toxins (PFTs). These toxins may be split into two groups: those where the membrane inserted pore is formed from α-helices and those where it is formed from β-strands (i.e., βPFTs). βPFTs are secreted as soluble monomer proteins, which, after binding to a receptor (protein or small molecule) at the cell surface, oligomerize and undergo significant conformation change such that each monomer extends a β-hairpin that contributes to the formation of the β-barrel pore. Clostridium perfringens is a ubiquitous, anaerobic bacterium that is responsible for a large number of diseases in humans and animals as a consequence of the array toxins that it secretes. Among these toxins, the βPFTs are overrepresented. We have investigated the structures and biophysical properties of a number of the C. perfringens toxins from the smaller βPFT superfamilies—namely, the hemolysin-like and aerolysin-like groups. In this chapter, we describe a number of these toxins and discuss how both the similarities to other group members and the differences among them illuminate their mechanism of action. The reason why such a wide arrays of βPFTs are produced by C. perfringens is not clear. However, the relative ease with which these toxins can be isolated allows valuable comparisons of their properties to be made. In this way, we may gain new insights into the ways in which the properties of toxins could be rationally engineered (for example, to generate novel toxins with therapeutic applications).