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. 1994 May 1;179(5):1653–1658. doi: 10.1084/jem.179.5.1653

Gene structure of the Helicobacter pylori cytotoxin and evidence of its key role in gastric disease

PMCID: PMC2191472  PMID: 8163943

Abstract

The gram negative, microaerophilic bacterium Helicobacter pylori colonizes the human gastric mucosa and establishes a chronic infection that is tightly associated with atrophic gastritis, peptic ulcer, and gastric carcinoma. Cloning of the H. pylori cytotoxin gene shows that the protein is synthesized as a 140-kD precursor that is processed to a 94-kD fully active toxin. Oral administration to mice of the purified 94-kD protein caused ulceration and gastric lesions that bear some similarities to the pathology observed in humans. The cloning of the cytotoxin gene and the development of a mouse model of human gastric disease will provide the basis for the understanding of H. pylori pathogenesis and the development of therapeutics and vaccines.

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Selected References

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  1. Blaser M. J. Gastric Campylobacter-like organisms, gastritis, and peptic ulcer disease. Gastroenterology. 1987 Aug;93(2):371–383. doi: 10.1016/0016-5085(87)91028-6. [DOI] [PubMed] [Google Scholar]
  2. Covacci A., Censini S., Bugnoli M., Petracca R., Burroni D., Macchia G., Massone A., Papini E., Xiang Z., Figura N. Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5791–5795. doi: 10.1073/pnas.90.12.5791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cover T. L., Blaser M. J. Helicobacter pylori and gastroduodenal disease. Annu Rev Med. 1992;43:135–145. doi: 10.1146/annurev.me.43.020192.001031. [DOI] [PubMed] [Google Scholar]
  4. Cover T. L., Blaser M. J. Purification and characterization of the vacuolating toxin from Helicobacter pylori. J Biol Chem. 1992 May 25;267(15):10570–10575. [PubMed] [Google Scholar]
  5. Cover T. L., Puryear W., Perez-Perez G. I., Blaser M. J. Effect of urease on HeLa cell vacuolation induced by Helicobacter pylori cytotoxin. Infect Immun. 1991 Apr;59(4):1264–1270. doi: 10.1128/iai.59.4.1264-1270.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cover T. L., Reddy L. Y., Blaser M. J. Effects of ATPase inhibitors on the response of HeLa cells to Helicobacter pylori vacuolating toxin. Infect Immun. 1993 Apr;61(4):1427–1431. doi: 10.1128/iai.61.4.1427-1431.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Crabtree J. E., Wyatt J. I., Sobala G. M., Miller G., Tompkins D. S., Primrose J. N., Morgan A. G. Systemic and mucosal humoral responses to Helicobacter pylori in gastric cancer. Gut. 1993 Oct;34(10):1339–1343. doi: 10.1136/gut.34.10.1339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dooley C. P., Cohen H., Fitzgibbons P. L., Bauer M., Appleman M. D., Perez-Perez G. I., Blaser M. J. Prevalence of Helicobacter pylori infection and histologic gastritis in asymptomatic persons. N Engl J Med. 1989 Dec 7;321(23):1562–1566. doi: 10.1056/NEJM198912073212302. [DOI] [PubMed] [Google Scholar]
  9. Klinkert M. Q., Ruppel A., Felleisen R., Link G., Beck E. Expression of diagnostic 31/32 kilodalton proteins of Schistosoma mansoni as fusions with bacteriophage MS2 polymerase. Mol Biochem Parasitol. 1988 Jan 15;27(2-3):233–239. doi: 10.1016/0166-6851(88)90042-4. [DOI] [PubMed] [Google Scholar]
  10. Nagata K., Mizuta T., Tonokatu Y., Fukuda Y., Okamura H., Hayashi T., Shimoyama T., Tamura T. Monoclonal antibodies against the native urease of Helicobacter pylori: synergistic inhibition of urease activity by monoclonal antibody combinations. Infect Immun. 1992 Nov;60(11):4826–4831. doi: 10.1128/iai.60.11.4826-4831.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Nicosia A., Bartoloni A., Perugini M., Rappuoli R. Expression and immunological properties of the five subunits of pertussis toxin. Infect Immun. 1987 Apr;55(4):963–967. doi: 10.1128/iai.55.4.963-967.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Papini E., Bugnoli M., De Bernard M., Figura N., Rappuoli R., Montecucco C. Bafilomycin A1 inhibits Helicobacter pylori-induced vacuolization of HeLa cells. Mol Microbiol. 1993 Jan;7(2):323–327. doi: 10.1111/j.1365-2958.1993.tb01123.x. [DOI] [PubMed] [Google Scholar]
  13. Parsonnet J., Friedman G. D., Vandersteen D. P., Chang Y., Vogelman J. H., Orentreich N., Sibley R. K. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991 Oct 17;325(16):1127–1131. doi: 10.1056/NEJM199110173251603. [DOI] [PubMed] [Google Scholar]
  14. Pugsley A. P. The complete general secretory pathway in gram-negative bacteria. Microbiol Rev. 1993 Mar;57(1):50–108. doi: 10.1128/mr.57.1.50-108.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rosenberg M., Court D. Regulatory sequences involved in the promotion and termination of RNA transcription. Annu Rev Genet. 1979;13:319–353. doi: 10.1146/annurev.ge.13.120179.001535. [DOI] [PubMed] [Google Scholar]
  16. Shine J., Dalgarno L. The 3'-terminal sequence of Escherichia coli 16S ribosomal RNA: complementarity to nonsense triplets and ribosome binding sites. Proc Natl Acad Sci U S A. 1974 Apr;71(4):1342–1346. doi: 10.1073/pnas.71.4.1342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Tricottet V., Bruneval P., Vire O., Camilleri J. P., Bloch F., Bonte N., Roge J. Campylobacter-like organisms and surface epithelium abnormalities in active, chronic gastritis in humans: an ultrastructural study. Ultrastruct Pathol. 1986;10(2):113–122. doi: 10.3109/01913128609014587. [DOI] [PubMed] [Google Scholar]
  18. Tummuru M. K., Cover T. L., Blaser M. J. Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: evidence of linkage to cytotoxin production. Infect Immun. 1993 May;61(5):1799–1809. doi: 10.1128/iai.61.5.1799-1809.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Xiang Z., Bugnoli M., Rappuoli R., Covacci A., Ponzetto A., Crabtree J. E. Helicobacter pylori: host responses in peptic ulceration. Lancet. 1993 Apr 3;341(8849):900–901. doi: 10.1016/0140-6736(93)93113-f. [DOI] [PubMed] [Google Scholar]

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