1.C.59 The Clostridium perfringens Enterotoxin (CPE) Family
C. perfringens uses an arsenal of 14 toxins to cause enteric and histotoxic infections in humans and domestic animals. One of these is CPE, also called heat-labile enterotoxin B chain precursor, possibly the most important of them from a medical standpoint. It forms complexes of variable sizes (~135, 155 and 200 kDa), but the 155 kDa complex alone causes 86Rb+ release and is probably responsible for the diarrheal and cramping symptoms of C. perfringens type A food poisoning. CPE also prevents tight junction formation, possibly by complexing the tight junction structural protein, occludin, in the 200 kDa complex. CPE is thus a bifunctional toxin which first generates pores (the 155 kDa complex) and then damages the tight junctions (the 200 kDa complex). It thus increases both cellular and paracellular permeability, thereby contributing to diarrhea of C. perfringens gastrointestinal disease. The Clostridium botulinum haemagglutinin/neurotoxin is 623 aas long (in contrast to CPE which is 309 aas long) and exhibits an internal repeat. Both repeats are about 24% identical to CPE. This toxin is composed of several subcomponents of ~53, 33, 23 and 17 kDa. Mature botulinum toxins are large and heterogeneous in size (Singh et al., 2001).
Upon its release from C. perfringens spores, CPE binds to its receptor, claudin, at the tight junctions between the epithelial cells of the gut wall and subsequently forms pores in the cell membranes. A number of different complexes between CPE and claudin have been observed. Briggs et al. (2011) have determined the three-dimensional structure of the soluble form of CPE in two crystal forms by X-ray crystallography, to a resolution of 2.7 and 4.0 Å, respectively, and found that the N-terminal domain shows structural homology with the aerolysin-like β-pore-forming family of proteins. They show that CPE forms a trimer in both crystal forms, and that this trimer is likely to be biologically relevant, although it is not the active pore form. The crystal structure of Clostridium perfringens enterotoxin displays features of beta-pore-forming toxins (Kitadokoro et al., 2011).
The transport reaction catalyzed by CPE is:
small molecules (in) small molecules (out)