1887

Abstract

Cytotoxic strains of cause an intense vacuolar degeneration of cells, due to the enlargement of late endosomes in the presence of membrane permeant weak bases. Bafilomycins, specific inhibitors of the vacuolar-type (V-) ATPase proton pump, prevent vacuole formation. The presence of the V-ATPase on vacuolar membranes was demonstrated by immunofluorescence with a monoclonal antibody (MAb) specific for the human 116-kDa regulatory subunit. The V-ATPase co-localised with the late endosomal marker rab7 on vacuolar membranes. In contrast, the early recycling endosomal compartment was not altered by the VacA cytotoxin, although it was endowed with the V-ATPase. Endocytosis of a MAb against the 116-kDa regulatory subunit of V-ATPase blocked endosomal acidification in HeLa cells and prevented VacA action. These results indicate that selective swelling of late endosomes, due to accumulation of osmotically active weak bases driven by the V-ATPase, is essential for vacuole formation.

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1996-08-01
2024-04-19
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References

  1. Warren J. R., Marshall B. J. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1983; 1:1273–1275
    [Google Scholar]
  2. Marshall B. J., Armstrong J. A., McGechie D. B., Glancy R. J. Attempt to fulfil Koch’s postulates for pyloric Campylobacter. Med J Aust 1985; 142:436–439
    [Google Scholar]
  3. Eurogast Study Group An international association between Helicobacter pylori infection and gastric cancer. Lancet 1993; 341:1359–1362
    [Google Scholar]
  4. N. I. H. Consensus Development Panel on Helicobacter pylori in peptic ulcer disease. JAMA 1994; 272:65–69
    [Google Scholar]
  5. Parsonnet J., Hansen S., Rodriguez L. Helicobacter pylori infection and gastric lymphoma. N Engl J Med 1994; 330:1267–1271
    [Google Scholar]
  6. Blaser M. J. Helicobacter pylori: microbiology of a “slow” bacterial infection. Trends Microbiol 1993; 1:255–260
    [Google Scholar]
  7. Telford J. L., Covacci A., Ghiara P., Montecucco C., Rappuoli R. Unravelling the pathogenic role of Helicobacter pylori in peptic ulcer: potential new therapies and vaccines. Trends Biotechnol 1994; 12:420–426
    [Google Scholar]
  8. Eaton K. A., Morgan D. R., Krakowka S. Motility as a factor in the colonisation of gnotobiotic piglets by Helicobacter pylori. J Med Microbiol 1992; 37:123–127
    [Google Scholar]
  9. Lingwood C. A. Helicobacter pylori′, receptors and adhesins. In Goodwin C. S., Worsely B. W. (eds) Helicobacter pylori, biology and clinical practice Boca Raton: FL, CRC Press; 1993209–222
    [Google Scholar]
  10. Boren T., Falk P., Roth K. A., Larson G., Normark S. Attachment of Helicobacter pylori to human gastric epithelium mediated by blood group antigens. Science 1993; 262:1892–1895
    [Google Scholar]
  11. Covacci A., Censini S., Bugnoli M. Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc Natl Acad Sci USA 1993; 90:5791–5795
    [Google Scholar]
  12. Crabtree J. E., Taylor J. D., Wyatt J. I. Mucosal IgA recognition of Helicobacter pylori 120 kDa protein, peptic ulceration, and gastric pathology. Lancet 1991; 338:332–335
    [Google Scholar]
  13. Marchetti M., Aricó, B., Burroni D., Figura N., Rappuoli R., Ghiara P. Development of a mouse model of Helicobacter pylori infection that mimics human disease. Science 1995; 267:1655–1658
    [Google Scholar]
  14. Cover T. L., Blaser M. J. Purification and characterization of the vacuolating toxin from Helicobacter pylori. J Biol Chem 1992; 267:10570–10575
    [Google Scholar]
  15. Telford J. L., Ghiara P., Dell’Orco M. Gene structure of the Helicobacter pylori cytotoxin and evidence of its key role in gastric disease. J Exp Med 1994; 179:1653–1658
    [Google Scholar]
  16. Phadnis S. H., Liver D., Janzon L., Normark S., Westblom T. U. Pathological significance and molecular characterization of the vacuolating toxin gene of Helicobacter pylori. Infect Immun 1994; 62:1557–1565
    [Google Scholar]
  17. Cover T. L., Tummuru M. K. R., Cao P., Thompson S. A., Blaser M. J. Divergence of genetic sequences for the vacuolating cytotoxin among Helicobacter pylori strains. J Biol Chem 1994; 269:10566–10573
    [Google Scholar]
  18. Schmitt W., Haas R. Genetic analysis of the Helicobacter pylori vacuolating cytotoxin: structural similarities with the IgA protease type of exported protein. Mol Microbiol 1994; 12:307–319
    [Google Scholar]
  19. Pugsley A. P. The complete general secretory pathway in gramnegative bacteria. Microbiol Rev 1993; 57:50–108
    [Google Scholar]
  20. Papini E., de Bernard M., Milia E. Cellular vacuoles induced by Helicobacter pylori originate from late endosomal compartments. Proc Natl Acad Sci USA 1994; 91:9720–9724
    [Google Scholar]
  21. Melhnan L., Fuchs R., Helenius A. Acidification of the endocytic and exocytic pathways. Ann Rev Biochem 1986; 55:663–700
    [Google Scholar]
  22. Nelson N. Organellar proton-ATPase. Curr Opin Cell Biol 1992; 4:654–660
    [Google Scholar]
  23. Bowman E. J., Siebers A., Altendorf K. Bafilomycins: a class of inhibitors of membrane ATPases from microorganisms, animal cells, and plant cells. Proc Natl Acad Sci USA 1988; 85:7972–7976
    [Google Scholar]
  24. Papini E., Bugnoli M., de Bernard M., Figura N., Rappuoli R., Montecucco C. Bafilomycin Al inhibits Helicobacter pylori- induced vacuolization of HeLa cells. Mol Microbiol 1993; 7:323–327
    [Google Scholar]
  25. Papini E., de Bernard M., Bugnoli M., Milia E., Rappuoli R., Montecucco C. Cell vacuolization induced by Helicobacter pylori′, inhibition by bafilomycins Al, Bl, Cl, and D. FEMS Microbiol Lett 1993; 113:155–159
    [Google Scholar]
  26. 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; 61:1427–1431
    [Google Scholar]
  27. Sato S. B., Toyama S. Interference with the endosomal acidification by a monoclonal antibody directed toward the 116 (100)-kD subunit of the vacuolar type proton pump. J Cell Biol 1994; 127:39–53
    [Google Scholar]
  28. Manetti R., Masari P., Burroni D. Helicobacter pylori cytotoxin: importance of native conformation for induction of neutralizing antibodies. Infect Immun 1995; 63:4476–4480
    [Google Scholar]
  29. Chavrier P., Parton G. R., Hauri H. P., Simons K., Zerial M. Localization of low molecular weight GTP binding proteins to exocytic and endocytic compartments. Cell 1990; 62:317–329
    [Google Scholar]
  30. Hopkins C. R., Trowbridge I. S. Internalization and processing of transferrin and the transferrin receptor in human carcinoma A431 cells. J Cell Biol 1983; 97:508–521
    [Google Scholar]
  31. Perin M. S., Fried V. A., Stone D. K., Xie X. S. Sudh of TC. Structure of the 116-kDa polypeptide of the chlatrin-coated vesicle synaptic vesicle proton pump. J Biol Chem 1991; 266:3877–3881
    [Google Scholar]
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