On the Interaction of Clostridium perfringens Enterotoxin with ClaudinsAuthor(s): Anna Veshnyakova | Jonas Protze | Jan Rossa | Ingolf E. Blasig | Gerd Krause | Joerg Piontek
Journal: Toxins ISSN 2072-6651
Volume: 2; Issue: 6; Start page: 1336; Date: 2010;
Keywords: Claudins | Clostridium perfringens enterotoxin | drug delivery | tight junction
Clostridium perfringens causes one of the most common foodborne illnesses, which is largely mediated by the Clostridium perfringens enterotoxin (CPE). The toxin consists of two functional domains. The N-terminal region mediates the cytotoxic effect through pore formation in the plasma membrane of the mammalian host cell. The C-terminal region (cCPE) binds to the second extracellular loop of a subset of claudins. Claudin-3 and claudin-4 have been shown to be receptors for CPE with very high affinity. The toxin binds with weak affinity to claudin-1 and -2 but contribution of these weak binding claudins to CPE-mediated disease is questionable. cCPE is not cytotoxic, however, it is a potent modulator of tight junctions. This review describes recent progress in the molecular characterization of the cCPE-claudin interaction using mutagenesis, in vitro binding assays and permeation studies. The results promote the development of recombinant cCPE-proteins and CPE-based peptidomimetics to modulate tight junctions for improved drug delivery or to treat tumors overexpressing claudins.