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. 1972 May;51(5):1212–1218. doi: 10.1172/JCI106915

The pathogenesis of Shigella Diarrhea

I. Enterotoxin production by Shigella dysenteriae 1

Gerald T Keusch 1,2, George F Grady 1,2, Leonardo J Mata 1,2, James McIver 1,2
PMCID: PMC292252  PMID: 4560429

Abstract

A strain of Shigella dysenteriae 1, freshly isolated from a patient with dysentery in Guatemala in August 1969, was found to elaborate an enterotoxin into the liquid of broth cultures. Partial purification of the enterotoxin by ultrafiltration on graded polymeric membranes and Sephadex gel filtration (Pharmacia Fine Chemicals, Inc., Piscataway, N. J.) suggested an approximate molecular weight of 55,000-60,000. The partially purified toxin was heat-labile, pronase sensitive, and activated by alkaline pH, and it elicited fluid production in ligated rabbit ileal segments; it failed, however, to cause increased vascular permeability in skin. When the activities of equal weights of identically prepared Vibrio cholerae and S. dysenteriae enterotoxins were compared in the rabbit ileum the latter caused a significantly smaller volume response with increased concentrations of potassium, chloride, and protein.

The previously described neurotoxic (mouse lethal) factor was also present and eluted from Sephadex G-150 with the enterotoxin. If these biological activities prove to be possessed by a single molecular species, it is suggested that it be renamed Shigella enterotoxin in recognition of the physiologically more relevant biological action.

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Selected References

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

  1. ARM H. G., FLOYD T. M., FABER J. E., HAYES J. R. USE OF LIGATED SEGMENTS OF RABBIT SMALL INTESTINE IN EXPERIMENTAL SHIGELLOSIS. J Bacteriol. 1965 Mar;89:803–809. doi: 10.1128/jb.89.3.803-809.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BRANHAM S. E., DACK G. M., RIGGS D. B. Studies with Shigella dysenteriae (Shiga). IV. Immunological reactions in monkeys to the toxins in isolated intestinal pouches. J Immunol. 1953 Jan;70(1):103–113. [PubMed] [Google Scholar]
  3. BRIDGWATER F. A., MORGAN R. S., ROWSON K. E., WRIGHT G. P. The neurotoxin of Shigella shigae: morphological and functional lesions produced in the central nervous system of rabbits. Br J Exp Pathol. 1955 Oct;36(5):447–453. [PMC free article] [PubMed] [Google Scholar]
  4. Barrett-Connor E., Connor J. D. Extraintestinal manifestations of shigellosis. Am J Gastroenterol. 1970 Mar;53(3):234–245. [PubMed] [Google Scholar]
  5. CAVANAGH J. B., HOWARD J. G., WHITBY J. L. The neurotoxin of Shigella shigae; a comparative study of the effects produced in various laboratory animals. Br J Exp Pathol. 1956 Jun;37(3):272–278. [PMC free article] [PubMed] [Google Scholar]
  6. DuPont H. L., Hornick R. B., Dawkins A. T., Snyder M. J., Formal S. B. The response of man to virulent Shigella flexneri 2a. J Infect Dis. 1969 Mar;119(3):296–299. doi: 10.1093/infdis/119.3.296. [DOI] [PubMed] [Google Scholar]
  7. FORMAL S. B., DAMMIN G. J., LABREC E. H., SCHNEIDER H. Experimental Shigella infections: characteristics of a fatal infection produced in guinea pigs. J Bacteriol. 1958 May;75(5):604–610. doi: 10.1128/jb.75.5.604-610.1958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. FORMAL S. B., LABREC E. H., SCHNEIDER H. PATHOGENESIS OF BACILLARY DYSENTERY IN LABORATORY ANIMALS. Fed Proc. 1965 Jan-Feb;24:29–34. [PubMed] [Google Scholar]
  9. Formal S. B., Kent T. H., Austin S., Labrec E. H. Fluorescent-antibody and histological study of vaccinated and control monkeys challenged with Shigella flexneri. J Bacteriol. 1966 Jun;91(6):2368–2376. doi: 10.1128/jb.91.6.2368-2376.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Grady G. F., Keusch G. T. Pathogenesis of bacterial diarrheas. I. N Engl J Med. 1971 Oct 7;285(15):831–841. doi: 10.1056/NEJM197110072851505. [DOI] [PubMed] [Google Scholar]
  11. HOWARD J. G. Observations on the intoxication produced in mice and rabbits by the neurotoxin of Shigella shigae. Br J Exp Pathol. 1955 Oct;36(5):439–446. [PMC free article] [PubMed] [Google Scholar]
  12. Kubota Y., Liu P. V. An enterotoxin of Pseudomonas aeruginosa. J Infect Dis. 1971 Jan;123(1):97–98. doi: 10.1093/infdis/123.1.97. [DOI] [PubMed] [Google Scholar]
  13. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  14. Labrec E. H., Schneider H., Magnani T. J., Formal S. B. EPITHELIAL CELL PENETRATION AS AN ESSENTIAL STEP IN THE PATHOGENESIS OF BACILLARY DYSENTERY. J Bacteriol. 1964 Nov;88(5):1503–1518. doi: 10.1128/jb.88.5.1503-1518.1964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Levin J., Bang F. B. Clottable protein in Limulus; its localization and kinetics of its coagulation by endotoxin. Thromb Diath Haemorrh. 1968 Mar 31;19(1):186–197. [PubMed] [Google Scholar]
  16. Mata L. J., Gangarosa E. J., Cáceres A., Perera D. R., Mejicanos M. L. Epidemic Shiga bacillus dysentery in Central America. I. Etiologic investigations in Guatemala, 1969. J Infect Dis. 1970 Sep;122(3):170–180. doi: 10.1093/infdis/122.3.170. [DOI] [PubMed] [Google Scholar]
  17. PROHASKA J. V., LONG E. T., NELSEN T. S. Pseudomembranous enterocolitis; its etiology and the mechanism of the disease process. AMA Arch Surg. 1956 Jun;72(6):977–983. [PubMed] [Google Scholar]
  18. 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]
  19. Swallow J. H., Code C. F., Freter R. Effect of cholera toxin on water and ion fluxes in the canine bowel. Gastroenterology. 1968 Jan;54(1):35–40. [PubMed] [Google Scholar]
  20. TAN T. L., DRAKE C. T., JACOBSON M. J., VAN PROHASKA J. The experimental development of pseudomembranous enterocolitis. Surg Gynecol Obstet. 1959 Apr;108(4):415–420. [PubMed] [Google Scholar]
  21. Takeuchi A., Sprinz H., LaBrec E. H., Formal S. B. Experimental bacillary dysentery. An electron microscopic study of the response of the intestinal mucosa to bacterial invasion. Am J Pathol. 1965 Dec;47(6):1011–1044. [PMC free article] [PubMed] [Google Scholar]
  22. VAN HEYNINGEN W. E., GLADSTONE G. P. The neurotoxin of Shigella shigae. I. Production, purification and properties of the toxin. Br J Exp Pathol. 1953 Apr;34(2):202–216. [PMC free article] [PubMed] [Google Scholar]
  23. WATTEN R. H., MORGAN F. M., YACHAI NA SONGKHLA, VANIKIATI B., PHILLIPS R. A. Water and electrolyte studies in cholera. J Clin Invest. 1959 Nov;38:1879–1889. doi: 10.1172/JCI103965. [DOI] [PMC free article] [PubMed] [Google Scholar]

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