On the Interaction of Clostridium perfringens Enterotoxin with Claudins

Toxins

Anna Veshnyakova¹  Jonas Protze¹  Jan Rossa¹  Ingolf E. Blasig¹  Gerd Krause¹ 

[1] Leibniz-Institut für molekulare Pharmakologie, Robert-Rössle-Str.10, 13125 Berlin, Germany;

关键词: Claudins;    Clostridium perfringens enterotoxin;    drug delivery;    tight junction;   

DOI  :  10.3390/toxins2061336

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2010 by the authors; licensee MDPI, Basel, Switzerland