Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1973 Mar 31;137(4):1009–1023. doi: 10.1084/jem.137.4.1009

DIFFERENTIAL INHIBITORY EFFECTS OF CHOLERA TOXOIDS AND GANGLIOSIDE ON THE ENTEROTOXINS OF VIBRIO CHOLERAE AND ESCHERICHIA COLI

Nathaniel F Pierce 1
PMCID: PMC2139228  PMID: 4571325

Abstract

Natural cholera toxoid appears to act as a competitive inhibitor of cholera enterotoxin and is thus a useful tool for studying the interaction of cholera enterotoxin with cell membranes. Cholera enterotoxin binds to gut mucosa more rapidly than does its natural toxoid. Once binding occurs, however, it appears to be prolonged for both materials. Formalinized cholera toxoid has no inhibitory effect upon cholera enterotoxin. Enterotoxic activity, ability to bind to gut mucosa, and antitoxigenicity appear to be independent properties of cholera enterotoxin. Natural cholera toxoid does not inhibit Escherichia coli enterotoxin, indicating that although the two enterotoxins activate the same mucosal secretory mechanism they occupy different binding sites in the mucosa. Ganglioside, which may be the mucosal receptor of cholera enterotoxin, is highly efficient in deactivating cholera enterotoxin. By contrast, ganglioside is relatively inefficient in deactivating heat-labile E. coli enterotoxin and is without effect upon the heat-stable component of E. coli enterotoxin. These findings suggest that ganglioside is not likely to be the mucosal receptor for E. coli enterotoxin. Differences in cellular binding of E. coli and cholera enterotoxins may explain, at least in part, the marked differences in the time of onset and duration of their effects upon gut secretion.

Full Text

The Full Text of this article is available as a PDF (831.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Banwell J. G., Gorbach S. L., Pierce N. F., Mitra R., Mondal A. Acute undifferentiated human diarrhea in the tropics. II. Alterations in intestinal fluid and electrolyte movements. J Clin Invest. 1971 Apr;50(4):890–900. doi: 10.1172/JCI106561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Carpenter C. C., Curlin G. T., Greenough W. B. Response of canine Thiry-Vella jejunal loops to cholera exotoxin and its modification by ethacrynic acid. J Infect Dis. 1969 Sep;120(3):332–338. doi: 10.1093/infdis/120.3.332. [DOI] [PubMed] [Google Scholar]
  3. Curlin G. T., Subong A., Craig J. P., Carpenter C. C. Antitoxic immunity in experimental canine cholera. Trans Assoc Am Physicians. 1968;81:314–322. [PubMed] [Google Scholar]
  4. DE S. N., CHATTERJE D. N. An experimental study of the mechanism of action of Vibriod cholerae on the intestinal mucous membrane. J Pathol Bacteriol. 1953 Oct;66(2):559–562. doi: 10.1002/path.1700660228. [DOI] [PubMed] [Google Scholar]
  5. Finkelstein R. A., LoSpalluto J. J. Pathogenesis of experimental cholera. Preparation and isolation of choleragen and choleragenoid. J Exp Med. 1969 Jul 1;130(1):185–202. doi: 10.1084/jem.130.1.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gorbach S. L., Banwell J. G., Chatterjee B. D., Jacobs B., Sack R. B. Acute undifferentiated human diarrhea in the tropics. I. Alterations in intestinal micrflora. J Clin Invest. 1971 Apr;50(4):881–889. doi: 10.1172/JCI106560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Guerrant R. L., Chen L. C., Sharp G. W. Intestinal adenyl-cyclase activity in canine cholera: correlation with fluid accumulation. J Infect Dis. 1972 Apr;125(4):377–381. doi: 10.1093/infdis/125.4.377. [DOI] [PubMed] [Google Scholar]
  8. Gyles C. L., Barnum D. A. A heat-labile enterotoxin from strains of Eschericha coli enteropathogenic for pigs. J Infect Dis. 1969 Oct;120(4):419–426. doi: 10.1093/infdis/120.4.419. [DOI] [PubMed] [Google Scholar]
  9. Harper D. T., Jr, Yardley J. H., Hendrix T. R. Reversal of cholera exotoxin-induced jejunal secretion by cycloheximide. Johns Hopkins Med J. 1970 May;126(5):258–266. [PubMed] [Google Scholar]
  10. Kimberg D. V., Field M., Johnson J., Henderson A., Gershon E. Stimulation of intestinal mucosal adenyl cyclase by cholera enterotoxin and prostaglandins. J Clin Invest. 1971 Jun;50(6):1218–1230. doi: 10.1172/JCI106599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Moon H. W., Whipp S. C., Engstrom G. W., Baetz A. L. Response of the rabbit ileal loop to cell-free products from Escherichia coli enteropathogenic for swine. J Infect Dis. 1970 Feb;121(2):182–187. doi: 10.1093/infdis/121.2.182. [DOI] [PubMed] [Google Scholar]
  12. Northrup R. S., Chisari F. V. Response of monkeys to immunization with cholera toxoid, toxin, and vaccine: reversion of cholera toxoid. J Infect Dis. 1972 May;125(5):471–479. doi: 10.1093/infdis/125.5.471. [DOI] [PubMed] [Google Scholar]
  13. Parkinson D. K., Ebel H., DiBona D. R., Sharp G. W. Localization of the action of cholera toxin on adenyl cyclase in mucosal epithelial cells of rabbit intestine. J Clin Invest. 1972 Sep;51(9):2292–2298. doi: 10.1172/JCI107039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Peterson J. W., LoSpalluto J. J., Finkelstein R. A. Localization of cholera toxin in vivo. J Infect Dis. 1972 Dec;126(6):617–628. doi: 10.1093/infdis/126.6.617. [DOI] [PubMed] [Google Scholar]
  15. Pierce N. F., Graybill J. R., Kaplan M. M., Bouwman D. L. Systemic effects of parenteral cholera enterotoxin in dogs. J Lab Clin Med. 1972 Jan;79(1):145–156. [PubMed] [Google Scholar]
  16. Pierce N. F., Kaniecki E. A., Northrup R. S. Protection against experimental cholera by antitoxin. J Infect Dis. 1972 Dec;126(6):606–616. doi: 10.1093/infdis/126.6.606. [DOI] [PubMed] [Google Scholar]
  17. Pierce N. F., Wallace C. K. Stimulation of jejunal secretion by a crude Escherichia coli enterotixin. Gastroenterology. 1972 Sep;63(6):439–448. [PubMed] [Google Scholar]
  18. Sack R. B., Gorbach S. L., Banwell J. G., Jacobs B., Chatterjee B. D., Mitra R. C. Enterotoxigenic Escherichia coli isolated from patients with severe cholera-like disease. J Infect Dis. 1971 Apr;123(4):378–385. doi: 10.1093/infdis/123.4.378. [DOI] [PubMed] [Google Scholar]
  19. Serebro H. A., Iber F. L., Yardley J. H., Hendrix T. R. Inhibition of cholera toxin action in the rabbit by cycloheximide. Gastroenterology. 1969 Mar;56(3):506–511. [PubMed] [Google Scholar]
  20. Sharp G. W., Hynie S. Stimulation of intestinal adenyl cyclase by cholera toxin. Nature. 1971 Jan 22;229(5282):266–269. doi: 10.1038/229266a0. [DOI] [PubMed] [Google Scholar]
  21. Smith H. W., Halls S. Studies on Escherichia coli enterotoxin. J Pathol Bacteriol. 1967 Apr;93(2):531–543. doi: 10.1002/path.1700930212. [DOI] [PubMed] [Google Scholar]
  22. VAN HEYNINGEN W. E., MILLER P. A. The fixation of tetanus toxin by ganglioside. J Gen Microbiol. 1961 Jan;24:107–119. doi: 10.1099/00221287-24-1-107. [DOI] [PubMed] [Google Scholar]
  23. Van Heyningen W. E., Carpenter C. C., Pierce N. F., Greenough W. B., 3rd Deactivation of cholera toxin by ganglioside. J Infect Dis. 1971 Oct;124(4):415–418. doi: 10.1093/infdis/124.4.415. [DOI] [PubMed] [Google Scholar]
  24. Vaughan M., Pierce N. F., Greenough W. B., 3rd Stimulation of glycerol production in fat cells by cholera toxin. Nature. 1970 May 16;226(5246):658–659. doi: 10.1038/226658a0. [DOI] [PubMed] [Google Scholar]
  25. Zieve P. D., Pierce N. F., Greenough W. B., 3rd Stimulation of glycogenolysis by purified cholera exotoxin in disrupted cells. Johns Hopkins Med J. 1971 Dec;129(6):299–303. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES