title: Comparative study of the nature and biological activities of bacterial enterotoxins.
abstract: It is apparent that there are considerable similarities between many of the enterotoxins produced by enteric pathogens. Although the effect of most of these toxins is restricted to the intestine in vivo, many cells are also sensitive to intoxication in vitro. The resultant in-vitro biochemical changes may have no pathological significance but serve to underline the central role of cyclic nucleotides in cellular fluid regulation. The biological activity of these enterotoxins is the result of interaction with membrane-bound adenylate cyclase, leading to persistent elevation of intracellular levels of cAMP. Stimulation of adenylate cyclase occurs consistently after a characteristic lag phase which varies somewhat between toxins. The duration and degree of stimulation of adenylate cyclase by the various toxins may point to possible differences in affinity, dissociation and mechanism of activation of the cyclase molecule. Subtle events at, or within, the cell membrane must occur during intoxication and may include complex associations of toxin with membrane lipid and protein components. The heat-labile toxins of V. cholerae, E. coli, Salmonella spp., A. hydrophila and Y. enterocolitica have much in common in their structures, membrane receptors and biochemical modes of action. Similarly the heat-stable toxins of E. coli and Y. enterocolitica, match each other in their biological activities. Classified along with the enterotoxin of C. perfringens, the enterotoxin produced by Sh. dysenteriae (and possibly some strains of E. coli) appears to differ from the other enterotoxins by acting on protein biosynthesis primarily and not on the nucleotide cyclase activation systems. In another category must be placed the various enterotoxins produced by Staph. aureus until more is known. Surprisingly little research has been directed towards the elucidation of their mode of action, although much is known of their serological and structural differences. Evidence to date suggests that staphylococcal enterotoxins differ from the other diarrhoeagenic agents discussed in this review. The structural and immunological similarities between the various heat-labile enterotoxins suggest a common genetic origin with gene transfer between the different bacterial species being responsible for the spread of enterotoxigenicity. It is possible that many of the "newer" enterotoxins owe their origin to genetic recombination with the "older" enteropathogens like V. cholerae.
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000333:Aeromonas; D000818:Animals; D001409:Bacillus cereus; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000494:pharmacology; D001826:Body Fluids / Q000378:metabolism; D002199:Capillary Permeability; D003013:Clostridium; D003016:Clostridium perfringens; D000242:Cyclic AMP / Q000378:metabolism; D004731:Endotoxins; D004768:Enterotoxins / Q000378:metabolism / Q000494:pharmacology*; D004926:Escherichia coli; D029968:Escherichia coli Proteins; D006162:Guanylate Cyclase; D007413:Intestinal Mucosa / Q000378:metabolism*; D008954:Models, Biological; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D011971:Receptors, Immunologic / Q000378:metabolism; D018000:Receptors, Peptide; D012475:Salmonella; D022603:Shiga Toxins; D012762:Shigella dysenteriae; D013211:Staphylococcus aureus; D014734:Vibrio cholerae; D015008:Yersinia enterocolitica
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004731:Endotoxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D022603:Shiga Toxins; C035598:enterotoxin, Clostridium; C034151:heat stable toxin (E coli); C027952:salmonella toxin; C037420:stN protein, Vibrio cholerae; C031815:toxB protein, Clostridium difficile; C027538:heat-labile enterotoxin, E coli; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled