The role of bacterial and non-bacterial toxins in the induction of changes in membrane transport: implications for diarrhea.

Abstract

Bacterial toxins induce changes in membrane transport which underlie the loss of electrolyte homeostasis associated with diarrhea. Bacterial- and their secreted toxin-types which have been linked with diarrhea include: (a) Vibrio cholerae (cholera toxin, E1 Tor hemolysin and accessory cholera enterotoxin); (b) Escherichia coli (heat stable enterotoxin, heat-labile enterotoxin and colicins); (c) Shigella dysenteriae (shiga-toxin); (d) Clostridium perfringens (C. perfringens enterotoxin, alpha-toxin, beta-toxin and theta-toxin); (e) Clostridium difficile (toxins A and B); (f) Staphylococcus aureus (alpha-haemolysin); (g) Bacillus cereus (cytotoxin K and haemolysin BL); and (h) Aeromonas hydrophila (aerolysin, heat labile cytotoxins and heat stable cytotoxins). The mechanisms of toxin-induced diarrhea include: (a) direct effects on ion transport in intestinal epithelial cells, i.e. direct toxin interaction with intrinsic ion channels in the membrane and (b) indirect interaction with ion transport in intestinal epithelial cells mediated by toxin binding to a membrane receptor. These effects consequently cause the release of second messengers, e.g. the release of adenosine 3',5'-cyclic monophosphate/guanosine 3',5'-monophosphate, IP(3), Ca2+ and/or changes in second messengers that are the result of toxin-formed Ca2+ and K+ permeable channels, which increase Ca2+ flux and augment changes in Ca2+ homeostasis and cause depolarisation of the membrane potential. Consequently, many voltage-dependent ion transport systems, e.g. voltage-dependent Ca2+ influx, are affected. The toxin-formed ion channels may act as a pathway for loss of fluid and electrolytes. Although most of the diarrhea-causing toxins have been reported to act via cation and anion channel formation, the properties of these channels have not been well studied, and the available biophysical properties that are needed for the characterization of these channels are inadequate.

• Authors: Karina N Laohachai, Randa Bahadi, Maria B Hardo, Phillip G Hardo, Joseph I Kourie
• Journal: Toxicon : official journal of the International Society on Toxinology (Toxicon) Vol. 42 Issue 7 Pg. 687-707 (Dec 2003) ISSN: 0041-0101 [Print] England
• PMID: 14757199 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Bacterial Toxins
• Electrolytes
• Ion Channels
• Toxins, Biological

Topics

• Bacterial Toxins (toxicity)
• Biological Transport (drug effects)
• Diarrhea (etiology, physiopathology)
• Electrolytes (metabolism)
• Gastrointestinal Tract (drug effects)
• Humans
• Ion Channels (drug effects)
• Toxins, Biological (toxicity)
• Water-Electrolyte Balance (drug effects)