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. 1987 Oct;55(10):2526–2530. doi: 10.1128/iai.55.10.2526-2530.1987

Production of a unique cytotoxin by Campylobacter jejuni.

R L Guerrant 1, C A Wanke 1, R A Pennie 1, L J Barrett 1, A A Lima 1, A D O'Brien 1
PMCID: PMC260740  PMID: 3653987

Abstract

Campylobacter jejuni is an important diarrheal pathogen worldwide; the mechanisms by which it causes disease remain unclear. Because of its association with inflammatory diarrhea, we postulated that C. jejuni might produce a cytotoxin similar to that produced by Shigella sp., enterohemorrhagic Escherichia coli O157, or Clostridium difficile. Filtrates of 12 polymyxin-treated isolates of C. jejuni were placed on HeLa cells (sensitive to Shiga toxin cytotoxicity) and Chinese hamster ovary (CHO) cells. Of 12 isolates of C. jejuni tested, 5 killed 50% of the cells at greater than or equal to 1:4 dilutions of filtered suspensions of 10(9) bacteria per ml; killing was similar in HeLa and CHO cells (the CHO cells being insensitive to Shiga cytotoxin). One isolate produced a titer of 1:32 to 1:128. The relative potency in HeLa cells was comparable to that of E. coli strains that produce intermediate amounts of Shiga-like toxin. The other seven strains showed no cytotoxic effect, nor did the control diluents, polymyxin B, or supernatants of C. jejuni not treated with polymyxin B. Sonication also released active cytotoxin, but slightly less well than did polymyxin. The cytotoxic effect was dose dependent. Concentration of the C. jejuni in suspension by 10-fold before treatment with polymyxin B resulted in a 10-fold increase in the 50% cytotoxic dose. The cytotoxin effect was not neutralized by Shiga toxin immune serum against either Shiga-like toxin I or II or by anti-Clostridium difficile antiserum. The C jejuni cytotoxin was partially labile to trypsin (0.25%) and to heating to greater than or equal to 60 degrees C. Cytotoxicity was retained in Scientific Products dialysis tubing D1615-1 (Mr cutoff, 12,000 to 14,000). Some isolates of C. jejuni release a substance lethal to HeLa or CHO cells in vitro that is distinct from Shiga-like or Clostridium difficile toxin. This cytotoxin may contribute to the colonic mucosal invasive process that characterizes C. jejuni enteritis.

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Selected References

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  1. BERNHEIMER A. W., SCHWARTZ L. L. Isolation and composition of staphylococcal alpha toxin. J Gen Microbiol. 1963 Mar;30:455–468. doi: 10.1099/00221287-30-3-455. [DOI] [PubMed] [Google Scholar]
  2. Blaser M. J., Berkowitz I. D., LaForce F. M., Cravens J., Reller L. B., Wang W. L. Campylobacter enteritis: clinical and epidemiologic features. Ann Intern Med. 1979 Aug;91(2):179–185. doi: 10.7326/0003-4819-91-2-179. [DOI] [PubMed] [Google Scholar]
  3. Blaser M. J., Glass R. I., Huq M. I., Stoll B., Kibriya G. M., Alim A. R. Isolation of Campylobacter fetus subsp. jejuni from Bangladeshi children. J Clin Microbiol. 1980 Dec;12(6):744–747. doi: 10.1128/jcm.12.6.744-747.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blaser M. J., Reller L. B. Campylobacter enteritis. N Engl J Med. 1981 Dec 10;305(24):1444–1452. doi: 10.1056/NEJM198112103052404. [DOI] [PubMed] [Google Scholar]
  5. Blaser M. J., Wells J. G., Feldman R. A., Pollard R. A., Allen J. R. Campylobacter enteritis in the United States. A multicenter study. Ann Intern Med. 1983 Mar;98(3):360–365. doi: 10.7326/0003-4819-98-3-360. [DOI] [PubMed] [Google Scholar]
  6. Bokkenheuser V. D., Richardson N. J., Bryner J. H., Roux D. J., Schutte A. B., Koornhof H. J., Freiman I., Hartman E. Detection of enteric campylobacteriosis in children. J Clin Microbiol. 1979 Feb;9(2):227–232. doi: 10.1128/jcm.9.2.227-232.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bokkenheuser V. Vibrio fetus infection in man. I. Ten new cases and some epidemiologic observations. Am J Epidemiol. 1970 Apr;91(4):400–409. doi: 10.1093/oxfordjournals.aje.a121150. [DOI] [PubMed] [Google Scholar]
  8. Butzler J. P., Skirrow M. B. Campylobacter enteritis. Clin Gastroenterol. 1979 Sep;8(3):737–765. [PubMed] [Google Scholar]
  9. Chamovitz B. N., Hartstein A. I., Alexander S. R., Terry A. B., Short P., Katon R. Campylobacter jejuni-associated hemolytic-uremic syndrome in a mother and daughter. Pediatrics. 1983 Feb;71(2):253–256. [PubMed] [Google Scholar]
  10. Dean A. G., Ching Y. C., Williams R. G., Harden L. B. Test for Escherichia coli enterotoxin using infant mice: application in a study of diarrhea in children in Honolulu. J Infect Dis. 1972 Apr;125(4):407–411. doi: 10.1093/infdis/125.4.407. [DOI] [PubMed] [Google Scholar]
  11. Dekeyser P., Gossuin-Detrain M., Butzler J. P., Sternon J. Acute enteritis due to related vibrio: first positive stool cultures. J Infect Dis. 1972 Apr;125(4):390–392. doi: 10.1093/infdis/125.4.390. [DOI] [PubMed] [Google Scholar]
  12. Fernández H., Neto U. F., Fernandes F., de Almeida Pedra M., Trabulsi L. R. Culture supernatants of Campylobacter jejuni induce a secretory response in jejunal segments of adult rats. Infect Immun. 1983 Apr;40(1):429–431. doi: 10.1128/iai.40.1.429-431.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Glass R. I., Stoll B. J., Huq M. I., Struelens M. J., Blaser M., Kibriya A. K. Epidemiologic and clinical features of endemic Campylobacter jejuni infection in Bangladesh. J Infect Dis. 1983 Aug;148(2):292–296. doi: 10.1093/infdis/148.2.292. [DOI] [PubMed] [Google Scholar]
  14. Guerrant R. L., Lahita R. G., Winn W. C., Jr, Roberts R. B. Campylobacteriosis in man: pathogenic mechanisms and review of 91 bloodstream infections. Am J Med. 1978 Oct;65(4):584–592. doi: 10.1016/0002-9343(78)90845-8. [DOI] [PubMed] [Google Scholar]
  15. Johnson W. M., Lior H. Toxins produced by Campylobacter jejuni and Campylobacter coli. Lancet. 1984 Jan 28;1(8370):229–230. doi: 10.1016/s0140-6736(84)92155-x. [DOI] [PubMed] [Google Scholar]
  16. KING E. O. Human infections with Vibrio fetus and a closely related vibrio. J Infect Dis. 1957 Sep-Oct;101(2):119–128. doi: 10.1093/infdis/101.2.119. [DOI] [PubMed] [Google Scholar]
  17. Klipstein F. A., Engert R. F. Immunological relationship of the B subunits of Campylobacter jejuni and Escherichia coli heat-labile enterotoxins. Infect Immun. 1985 Jun;48(3):629–633. doi: 10.1128/iai.48.3.629-633.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Klipstein F. A., Engert R. F. Properties of crude Campylobacter jejuni heat-labile enterotoxin. Infect Immun. 1984 Aug;45(2):314–319. doi: 10.1128/iai.45.2.314-319.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Klipstein F. A., Engert R. F., Short H. B. Enzyme-linked immunosorbent assays for virulence properties of Campylobacter jejuni clinical isolates. J Clin Microbiol. 1986 Jun;23(6):1039–1043. doi: 10.1128/jcm.23.6.1039-1043.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Klipstein F. A., Engert R. F., Short H., Schenk E. A. Pathogenic properties of Campylobacter jejuni: assay and correlation with clinical manifestations. Infect Immun. 1985 Oct;50(1):43–49. doi: 10.1128/iai.50.1.43-49.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lior H. New, extended biotyping scheme for Campylobacter jejuni, Campylobacter coli, and "Campylobacter laridis". J Clin Microbiol. 1984 Oct;20(4):636–640. doi: 10.1128/jcm.20.4.636-640.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lior H., Woodward D. L., Edgar J. A., Laroche L. J., Gill P. Serotyping of Campylobacter jejuni by slide agglutination based on heat-labile antigenic factors. J Clin Microbiol. 1982 May;15(5):761–768. doi: 10.1128/jcm.15.5.761-768.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. McCardell B. A., Madden J. M., Lee E. C. Production of cholera-like toxin by Campylobacter jejuni/coli. Lancet. 1984 Feb 25;1(8374):448–449. doi: 10.1016/s0140-6736(84)91772-0. [DOI] [PubMed] [Google Scholar]
  24. McCardell B. A., Madden J. M., Shah D. B. Isolation and characterization of a cytolysin produced by Vibrio cholerae serogroup non-O1. Can J Microbiol. 1985 Aug;31(8):711–720. doi: 10.1139/m85-135. [DOI] [PubMed] [Google Scholar]
  25. McCardell B. A., Madden J. M., Stanfield J. T. Production of cytotoxins by Campylobacter. Lancet. 1986 May 3;1(8488):1031–1031. doi: 10.1016/s0140-6736(86)91297-3. [DOI] [PubMed] [Google Scholar]
  26. O'Brien A. D., Lively T. A., Chang T. W., Gorbach S. L. Purification of Shigella dysenteriae 1 (Shiga)-like toxin from Escherichia coli O157:H7 strain associated with haemorrhagic colitis. Lancet. 1983 Sep 3;2(8349):573–573. doi: 10.1016/s0140-6736(83)90601-3. [DOI] [PubMed] [Google Scholar]
  27. Olsvik O., Wachsmuth K., Morris G., Feeley J. C. Genetic probing of Campylobacter jejuni for cholera toxin and Escherichia coli heat-labile enterotoxin. Lancet. 1984 Feb 25;1(8374):449–449. doi: 10.1016/s0140-6736(84)91773-2. [DOI] [PubMed] [Google Scholar]
  28. Pennie R. A., Pearson R. D., Barrett L. J., Lior H., Guerrant R. L. Susceptibility of Campylobacter jejuni to strain-specific bactericidal activity in sera of infected patients. Infect Immun. 1986 Jun;52(3):702–706. doi: 10.1128/iai.52.3.702-706.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pennie R. A., Zunino J. N., Rose C. E., Jr, Guerrant R. L. Economical, simple method for production of the gaseous environment required for cultivation of Campylobacter jejuni. J Clin Microbiol. 1984 Sep;20(3):320–322. doi: 10.1128/jcm.20.3.320-322.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Riley L. W., Finch M. J. Results of the first year of national surveillance of Campylobacter infections in the United States. J Infect Dis. 1985 May;151(5):956–959. doi: 10.1093/infdis/151.5.956. [DOI] [PubMed] [Google Scholar]
  31. Ruiz-Palacios G. M., Escamilla E., Torres N. Experimental Campylobacter diarrhea in chickens. Infect Immun. 1981 Oct;34(1):250–255. doi: 10.1128/iai.34.1.250-255.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Ruiz-Palacios G. M., López-Vidal Y., Torres J., Torres N. Serum antibodies to heat-labile enterotoxin of Campylobacter jejuni. J Infect Dis. 1985 Aug;152(2):413–416. doi: 10.1093/infdis/152.2.413. [DOI] [PubMed] [Google Scholar]
  33. Ruiz-Palacios G. M., Torres J., Torres N. I., Escamilla E., Ruiz-Palacios B. R., Tamayo J. Cholera-like enterotoxin produced by Campylobacter jejuni. Characterisation and clinical significance. Lancet. 1983 Jul 30;2(8344):250–253. doi: 10.1016/s0140-6736(83)90234-9. [DOI] [PubMed] [Google Scholar]
  34. Skirrow M. B. Campylobacter enteritis: a "new" disease. Br Med J. 1977 Jul 2;2(6078):9–11. doi: 10.1136/bmj.2.6078.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Smith H. R., Day N. P., Scotland S. M., Gross R. J., Rowe B. Phage-determined production of vero cytotoxin in strains of Escherichia coli serogroup O157. Lancet. 1984 Jun 2;1(8388):1242–1243. doi: 10.1016/s0140-6736(84)91729-x. [DOI] [PubMed] [Google Scholar]
  36. Stoll B. J., Glass R. I., Banu H., Huq M. I., Khan M. U., Ahmed M. Value of stool examination in patients with diarrhoea. Br Med J (Clin Res Ed) 1983 Jun 25;286(6383):2037–2040. doi: 10.1136/bmj.286.6383.2037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Strockbine N. A., Marques L. R., Newland J. W., Smith H. W., Holmes R. K., O'Brien A. D. Two toxin-converting phages from Escherichia coli O157:H7 strain 933 encode antigenically distinct toxins with similar biologic activities. Infect Immun. 1986 Jul;53(1):135–140. doi: 10.1128/iai.53.1.135-140.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Thorson S. M., Lohr J. A., Dudley S., Guerrant R. L. Value of methylene blue examination, dark-field microscopy, and carbol-fuchsin Gram stain in the detection of Campylobacter enteritis. J Pediatr. 1985 Jun;106(6):941–943. doi: 10.1016/s0022-3476(85)80245-6. [DOI] [PubMed] [Google Scholar]
  39. Walker R. I., Caldwell M. B., Lee E. C., Guerry P., Trust T. J., Ruiz-Palacios G. M. Pathophysiology of Campylobacter enteritis. Microbiol Rev. 1986 Mar;50(1):81–94. doi: 10.1128/mr.50.1.81-94.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Yeen W. P., Puthucheary S. D., Pang T. Demonstration of a cytotoxin from Campylobacter jejuni. J Clin Pathol. 1983 Nov;36(11):1237–1240. doi: 10.1136/jcp.36.11.1237. [DOI] [PMC free article] [PubMed] [Google Scholar]

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