Skip to main content
SpringerLink
Log in

Helicobacter pylori Vacuolating Cytotoxin: Cell Intoxication and Anion-Specific Channel Activity

  • Chapter
Pore-Forming Toxins

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 257))

Abstract

The entire sequence of the circular genome of two Helicobacter pylori strains is presently available (Tomb et al. 1997; Alm et al. 1999), together with portions of the genome of several other strains. These genomes are predicted to contain about 1,500 coding genes, most of which encode proteins necessary for the formation, growth and division of the bacterial cell (Doig et al. 1999; Ge and Taylor 1999; Marais et al. 1999). Fewer genes, including those for urease and the proteins involved in its biosynthesis, are necessary for the colonization, binding and survival of H. pylori in its particular ecological niche, i.e., the apical surface of stomach epithelial cells and the protective mucus layer covering them. H. pylori can survive the acidic conditions of the stomach lumen by buffering the pH around itself through the action of the cytosolic urease, which catalyzes the hydrolysis of urea to produce ammonia (Weeks et al. 2000). H. pylori then rapidly enters the mucus layer which covers and protects the mucosa from the gastric fluid, preventing its ulceration. This layer has unique barrier properties, being rather impermeable even to small molecules. In addition, hydrogen ions can freely diffuse from the apical portion of the mucosal epithelial cells into the gastric lumen, but not vice-versa. In contrast, bicarbonate anions are poorly permeable, as is thought to be the case for iron and nickel ions, which are necessary for H. pylori growth. Thus, a pH gradient exists inside the mucus film, with the apical cell membrane being almost neutral under normal conditions, but becoming acid if the thickness of the protective layer is reduced.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Al-Awqati Q, Barasch J, Landry D (1992) Chloride channels of intracellular organelles and their potential role in cystic fibrosis. J Exp Biol 172:245–266

    PubMed  CAS  Google Scholar 

  • Aim RA, Ling L-SL, Moir DT, King BL, Brown ED, Doig PC, Smith DR, Noonan B, et al. (1999) Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature 397:176–180

    Article  Google Scholar 

  • Atherton JC, Cao P, Peek RM Jr, Tummuru MK, Blaser MJ, Cover TL (1995) Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem 270:17771–17777

    Article  PubMed  CAS  Google Scholar 

  • Blaser MJ (1993) Helicobacter pylori: microbiology of a “slow” bacterial infection. Trends Microbiol 1:255–259

    Article  PubMed  CAS  Google Scholar 

  • Boren T, Normark S, Falk P (1994) Helicobacter pylori: molecular basis for host recognition and bacterial adherence. Trends Microbiol 2:221–228

    Article  PubMed  CAS  Google Scholar 

  • Burroni D, Lupetti P, Pagliaccia C, Reyrat JM, Dallai R, Rappuoli R, Telford JL (1998) deletion of the major proteolytic site of the Helicobacter pylori cytotoxin does not influence toxin activity but favors assembly of the toxin into hexameric structures. Infect Immun 66:5547–5550

    PubMed  CAS  Google Scholar 

  • Catrenich CE, Chestnut MH (1992) Character and origin of vacuoles induced in mammalian cells by the cytotoxin of Helicobacter pylori. J Med Microbiol 37:389–395

    Article  PubMed  CAS  Google Scholar 

  • Covacci A, Telford JL, Del Giudice G, Parsonnet J, Rappuoli R (1999) Helicobacter pylori virulence and genetic geography. Science 284:1328–1333

    Article  PubMed  CAS  Google Scholar 

  • Cover TL (1996) The vacuolating cytotoxin of Helicobacter pylori. Mol Microbiol 20:241–246

    Article  PubMed  CAS  Google Scholar 

  • Cover TL, Blaser MJ (1992) Purification and characterization of the vacuolating toxin from Helicobacter pylori. J Biol Chem 267:10570–10575

    PubMed  CAS  Google Scholar 

  • Cover TL, Susan AH, Blaser MJ (1992) Characterization of HeLa cell vacuoles induced by Helicobacter pylori broth culture supernatant. Human Pathol 23:1004–1010

    Article  CAS  Google Scholar 

  • Cover TL, Reddy LY, Blaser MJ (1993) Effects of ATPase inhibitors on the response of HeLa cells to Helicobacter pylori vacuolating toxin. Infect Immun 61:1427–1431

    PubMed  CAS  Google Scholar 

  • Cover TL, Tummuru MKR, Cao P, Thompson SA, Blaser MJ (1994) Divergence of genetic sequences for the vacuolating cytotoxin among Helicobacter pylori strains. J Biol Chem 269:10566–10573

    PubMed  CAS  Google Scholar 

  • Cover TL, Hanson PI, Heuser JE (1997) Acid-induced dissociation of VacA, the Helicobacter pylori vacuolating toxin, reveals its pattern of assembly. J Cell Biol 138:759–769

    Article  PubMed  CAS  Google Scholar 

  • Czajkowsky DM, Iwamoto H, Cover TL, Shao Z (1999)The vacuolating toxin from Helicobacter pylori forms hexameric pores in lipid bilayers at low pH Proc Natl Acad Sci USA 96:2001–2006

    Article  PubMed  CAS  Google Scholar 

  • Dawson DC, Smith SS, Mansoura MK (1999) CFTR: mechanism of anion conduction. Physiol Rev 79:S47–S75

    PubMed  CAS  Google Scholar 

  • De Bernard M, Papini E, de Filippis V, Gottardi E, Telford JL, Manetti R, Fontana A, Rappuoli R, Montecucco C (1995) Low pH activates the vacuolating toxin of Helicobacter pylori, which becomes acid and pepsin resistant. J Biol Chem 270:23937–23940

    Article  PubMed  Google Scholar 

  • De Bernard M, Arico B, Papini E, Rizzuto R, Grandi G, Rappuoli R, Montecucco C (1997) Helicobacter pylori toxin VacA induces vacuoles formation by acting in the cell cytosol. Mol Microbiol 26:665–674

    Article  PubMed  Google Scholar 

  • De Bernard M, Moschioni M, Papini E, Telford J, Rappuoli R, Montecucco C (1998a) Cell vacuolization induced by Helicobacter pylori VacA toxin: cell line sensitivity and quantitative extimation. Toxicol Lett 99:109–115

    Article  PubMed  Google Scholar 

  • De Bernard M, Burroni D, Papini E, Rappuoli R, Telford JL, Montecucco C (1998b) Identification of the Helicobacter pylori VacA toxin domain active in the cell cytosol. Infect Immun 66:6014–6016

    PubMed  Google Scholar 

  • Dytoc M, Gold B, Louie M, Huesca M, Fedorko L, Crowe S, Lingwood C, Brunton J, Sherman P (1993) Comparison of Helicobacter pylori and attaching-effacing Escherichia coli adhesion to eukaryotic cells. Infect Immun 61:448–456 Eaton S, Simons K (1995) Apical, basal, lateral cues for epithelial polarization. Cell 82:5–8

    PubMed  CAS  Google Scholar 

  • Eisenman G, Horn R (1983) Ionic selectivity revisited: the role of kinetic and equilibrium processes in ion permeation through channels. J Membr Biol 76:197–225

    Article  PubMed  CAS  Google Scholar 

  • Figura N, Guglielmetti P, Rossolini A, Barberi A, Cusi G, Musmanno RA, Russi M, Quaranta S (1989) Cytotoxin production by Campylobacter pylori strains isolated from patients with peptic ulcers and from patients with chronic gastritis only. J Clin Microbiol 27:225–226

    PubMed  CAS  Google Scholar 

  • Fiocca R, Luinetti O, Villani L, Chiaravalli AM, Capella C, Solcia E (1994) Epithelial cytotoxicity, immune responses, inflammatory components of Helicobacter pylori gastritis. Scand J Gastroenterol 205:11–21

    Article  CAS  Google Scholar 

  • Fiocca R, Necchi V, Sommi P, Ricci V, Telford JL, Cover TL, Solcia E (1999) Release of Helicobacter pylori vacuolating cytotoxin by both a specific secretion pathway and budding of outer membrane vesicles. Uptake of released toxin and vesicles by gastric epithelium. J Pathol 188:220–226

    Article  PubMed  CAS  Google Scholar 

  • Garner J A, Cover TL (1996) Binding and internalization of the Helicobacter pylori vacuolating cytotoxin by epithelial cells. Infect Immun 64:4197–4203

    PubMed  CAS  Google Scholar 

  • Ge Z, Taylor DE (1999) Contributions of genome sequencing to understanding the biology of Helicobacter pylori. Annu Rev Microbiol 53:353–387

    Article  PubMed  CAS  Google Scholar 

  • Goodwin CS (1997) Helicobacter pylori gastritis, peptic ulcer, gastric cancer: clinical and molecular aspects. Clin Infect Dis 25:1017–1019

    Article  PubMed  CAS  Google Scholar 

  • Guarino A, Bisceglia M, Canani RB, Boccia MC, Mallardo G, Bruzzese E, Massari P, Rappuoli R, Telford JL (1998) Enterotoxic effect of the vacuolating toxin produced by Helicobacter pylori in Caco-2 cells. J Infect Dis 178:1373–1378

    Article  PubMed  CAS  Google Scholar 

  • Halter R, Pohlner J, Meyer TF (1989) Mosaic-like organization of IgA protease genes in Neisseria gonorrhoeae generated by horizontal genetic exchange in vivo. EMBO J 8:2737–2744

    PubMed  CAS  Google Scholar 

  • Hille B (1992) Ionic channels of excitable membranes. Sinauer, Sunderland, MA

    Google Scholar 

  • Iwamoto H, Czajkowsky DM, Cover TL, Szabó G, Shao Z (1999) VacA from Helicobacter pylori: a hexameric chloride channel. FEBS Lett: 450:101–104

    Article  PubMed  CAS  Google Scholar 

  • Kornfeld S, Mellman I (1989) The biogenesis of lysosomes. Annu Rev Cell Biol 5:483–525

    Article  PubMed  CAS  Google Scholar 

  • Kraehenbuhl JP, Neutra MR (1992) Molecular and cellular basis of immune protection of mucosal surfaces. Physiol Rev 72:853–879

    PubMed  CAS  Google Scholar 

  • Lanzavecchia S, Bellon PL, Lupetti P, Dallai R, Rappuoli R, Telford JL (1998) Three-dimensional reconstruction of metal replicas of the Helicobacter pylori vacuolating cytotoxin. J Struct Biol 121:9–18

    Article  PubMed  CAS  Google Scholar 

  • Leunk RD, Johnson PT, David BC, Kraft WG, Morgan DR (1988) Cytotoxin activity in broth-culture filtrates of Campylobacter pylori. J Med Microbiol 26:93–99

    Article  PubMed  CAS  Google Scholar 

  • Lupetti P, Heuser JE, Manetti R, Lanzavecchia S, Bellon PL, Dallai R, Rappuoli R, Telford JL (1996) Oligomeric and subunit structure of the Helicobacter pylori vacuolating cytotoxin. J Cell Biol 133:801–807

    Article  PubMed  CAS  Google Scholar 

  • Mai UE, Perez-Perez GI, Allen JB, Wahl SM, Blaser MJ, Smith PD (1992) Surface proteins from Helicobacter pylori exhibit chemotactic activity for human leukocytes and are present in gastric mucosa. J Exp Med 175:517–525

    Article  PubMed  CAS  Google Scholar 

  • Manetti R, Massari P, Burroni D, De Bernard M, Marchini A, Olivieri R, Papini E, Montecucco C, Rappuoli R, Telford JL (1995) Helicobacter pylori cytotoxin: importance of native conformation for induction of neutralizing antibodies. Infect Immun 63:4476–4480

    PubMed  CAS  Google Scholar 

  • Marais A, Mendz GL, Hazell SL, Megraud F (1999) Metabolism and genetics of Helicobacter pylori: the genome era. Microbiol Mol Biol Rev 63:642–674

    PubMed  CAS  Google Scholar 

  • Marchetti M, Arico B, Burroni D, Figura N, Rappuoli R, Ghiara P (1995) Development of a mouse model of Helicobacter pylori infection that mimics human disease. Science 265:1656–1658

    Google Scholar 

  • Marshall BJ, Armstrong JA, McGeche DB, Glancy RJ (1985) Attempt to fulfill Koch’s postulates for pyloric Campylobacter. Med J Aust 142:436–439

    PubMed  CAS  Google Scholar 

  • Molinari M, Galli C, Norais N, Telford JL, Rappuoli R, Luzio JP, Montecucco C (1997) Vacuoles induced by Helicobacter pylori toxin contain both late endosomal and lysosomal markers. J Biol Chem 272:25339–25344

    Article  PubMed  CAS  Google Scholar 

  • Molinari M, Galli C, De Bernard M, Norais N, Ruysschaert JM, Rappuoli R, Montecucco C (1998a) The acid activation of Helicobacter pylori toxin VacA: structural and membrane binding studies. Biochem Biophys Res Comun 248:334–340

    Article  CAS  Google Scholar 

  • Molinari M, Salio M, Galli C, Norais N, Rappuoli R, Lanzavecchia A, Montecucco C (1998b) Selective inhibition of Li-dependent antigen presentation by Helicobacter pylori toxin VacA. J Exp Med 187:135–140

    Article  PubMed  CAS  Google Scholar 

  • Moll G, Papini E, Colonna R, Burroni D, Telford JL, Rappuoli R, Montecucco C (1995) Lipid interaction of the 37-kDa and 58-kDa fragments of the Helicobacter pylori cytotoxin. Eur J Biochem 234:947–952

    Article  PubMed  CAS  Google Scholar 

  • Montecucco C, Papini E, De Bernard M, Zoratti M (1999a) Molecular and cellular activities of Helicobacter pylori pathogenic factors. FEBS Lett 452:16–21 Montecucco C, Papini E, De Bernard M, Telford JL, Rappuoli R (1999b) Helicobacter pylori vacuolating cytotoxin and associated pathogenic factors. In: Alouf Je, Freer JH (eds) The comprehensive sourcebook of bacterial protein toxins. Academic, San Diego CA 92:101

    Google Scholar 

  • Mukherjee S, Richik NG, Maxfield FR (1997) Endocytosis. Physiol Rev 77:759–803

    PubMed  CAS  Google Scholar 

  • Odenbreit S, Puis J, Sedlmaier B, Gerland E, Fischer W, Haas R (2000) Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science 287:1497–1500

    Article  PubMed  CAS  Google Scholar 

  • Pagliaccia C, De Bernard M, Lupetti P, Ji X, Burroni D, Cover TL, Papini E, Rappuoli R, Telford JL, Reyrat JM (1998) The m2 form of the Helicobacter pylori cytotoxin has cell type-specific vacuolating activity. Proc Natl Acad Sci USA 95:10212–10217

    Article  PubMed  CAS  Google Scholar 

  • Pagliaccia C, Wang XM, Tardy F, Telford JL, Ruysschaert JM, Cabiaux V (2000) Structure and interaction of VacA of Helicobacter pylori with a lipid membrane. Eur J Biochem 267:104–109

    Article  PubMed  CAS  Google Scholar 

  • Papini E, Bugnoli M, De Bernard M, Figura N, Rappuoli R, Montecucco C (1993) Bafomycin Al inhibits Helicobacter /jy/on-induced vacuolization of HeLa cells. Mol Microbiol 7:323–327

    Article  PubMed  CAS  Google Scholar 

  • Papini E, De Bernard M, Milia E, Zerial M, Rappuoli R, Montecucco C (1994) Cellular vacuoles induced by Helicobacter pylori originate from late endosomal compartments. Proc Natl Acad Sci USA 91:9720–9724

    Article  PubMed  CAS  Google Scholar 

  • Papini E, Gottardi E, Satin B, De Bernard M, Telford JL, Massari P, Rappuoli R, Sato SB, Montecucco C (1996) The vacuolar ATPase proton pump on intracellular vacuoles induced by Helicobacter pylori. J Med Microbiol 44:1–6

    Article  Google Scholar 

  • Papini E, Satin B, Bucci C, De Bernard M, Telford JL, Manetti R, Rappuoli R, Zerial M, Montecucco C (1997) The small GTP binding protein rab7 is essential for cellular vacuolation induced by Helicobacter pylori cytotoxin. EMBO J 16:15–24

    Article  PubMed  CAS  Google Scholar 

  • Papini E, Satin B, Norais N, De Bernard M, Telford JL, Rappuoli R, Montecucco C (1998) Selective increase of the permeability of polarized epithelial cell monolayers by Helicobacter pylori vacuolating toxin. J Clin Invest 102:813–820

    Article  PubMed  CAS  Google Scholar 

  • Pelicic V, Reyrat JM, Sartori L, Pagliaccia C, Rappuoli R, Telford JL Montecucco C, Papini E (1999) Helicobacter pylori VacA cytotoxin associated with the bacteria increases epithelial permeability independently of its vacuolating activity. Microbiology 145:2043–2050

    Article  PubMed  CAS  Google Scholar 

  • Phadnis SH, Liver D, Janzon L, Normark S, Westblom TU (1994) Pathological significance and molecular characterization of the vacuolating toxin gene of Helicobacter pylori. Infect Immun 62:1557–1565

    PubMed  CAS  Google Scholar 

  • Pohlner J, Halter R, Beyreuther K, Meyer TF (1987) Gene structure and extracellular secretion of Neisseria gonorrhoeae IgA protease. Nature 325:458–462

    Article  PubMed  CAS  Google Scholar 

  • Reyrat JM, Charrel M, Pagliaccia C, Burroni D, Lupetti P, De Bernard M, Xi J, Norais N, Papini E, Dallai R, Rappuoli R, Telford JL (1998) Characterization of a monoclonal antibody and its use to purify the cytotoxin of Helicobacter pylori FEMS Lett 165:79–84

    Article  CAS  Google Scholar 

  • Reyrat JM, Lanzavecchia S, Lupetti P, De Bernard M, Pagliaccia C, Pelicic V, Charrel M, Ulivieri C, Norais N, Ji X, Cabiaux V, Papini E, Rappuoli R, Telford JL (1999) 3D imaging of the 58kDa cell binding subunit of the Helicobacter pylori cytotoxin. J Mol Biol 290:459–470

    Article  PubMed  CAS  Google Scholar 

  • Ricci V, Sommi P, Fiocca R, Romano M, Solcia E, Ventura U (1997) Helicobacter pylori vacuolating toxin accumulates within the endosomal-vacuolar compartment of cultured gastric cells and potentiates the vacuolating activity of ammonia. J Pathol 183:453–459

    Article  PubMed  CAS  Google Scholar 

  • Sano K, Hayakawa A, Piao JH, Kosaka Y, Nakamura H (2000) Novel SH3 protein encoded by the AF3p21 gene is fused to the mixed lineage leukemia protein in a therapy-related leukemia with t(3;11) (p21;q23) Blood 95:1066–1068

    PubMed  CAS  Google Scholar 

  • Satin B, Norais N, Telford JL, Rappuoli R, Murgia M, Montecucco C, Papini E (1997) Vacuolating toxin of Helicobacter pylori inhibits maturation of procathepsin D and degradation of epidermal growth factor in HeLa cells through a partial neutralization of acidic intracellular compartments. J Biol Chem 272:25022–25028

    Article  PubMed  CAS  Google Scholar 

  • Schmitt W, Haas R (1994) Genetic analysis of the Helicobacter pylori vacuolating cytotoxin: structural similarities with the IgA protease type of exported protein. Mol Microbiol 12:307–319

    Article  PubMed  CAS  Google Scholar 

  • Segal ED, Falkow S, Tompkins LS (1996) Helicobacter pylori attachment to gastric cells induces cytoskeletal rearrangements and tyrosine phosphorylation of host cell proteins. Proc Natl Acad Sci USA 93:1259–1264

    Article  PubMed  CAS  Google Scholar 

  • Slomiany BL, Slomiany A (1991) Role of mucus in gastric mucosal protection J Physiol Pharmacol 42:147–161

    PubMed  CAS  Google Scholar 

  • Smoot DT, Resau JH, Naab T, Desbordes BC, Gilliam T, Bull-Henry K, et al. (1993) Adherence of Helicobacter pylori to cultured human gastric epithelial cells. Infect Immun 61:350–355

    PubMed  CAS  Google Scholar 

  • Steinert M, Hentschel U, Hacker J (2000) Symbiosis and pathogenesis: evolution of the microbe-host interaction. Naturwissenschaften 87:1–111

    Article  PubMed  CAS  Google Scholar 

  • Szabó I, Brutsche S, Tombola F, Moschioni M, Satin B, Telford JL, Rappuoli R, Montecucco C, Papini E, Zoratti M (1999) Formation of anion-selective channels in the cell plasma membrane by the toxin VacA of Helicobacter pylori is required for its biological activity. EMBO J 18:5517–5527

    Article  PubMed  Google Scholar 

  • Telford JL, Ghiara P, Dell’Orco M, Comanducci M, Burroni D, Bugnoli M, et al. (1994) Purification and characterization of the vacuolating toxin from Helicobacter pylori. J Exp Med 179:1653–1658

    Article  PubMed  CAS  Google Scholar 

  • Tomb JF, White O, Kerlavage AR, Clayton RA, Sutton GG, Fleischmann RD, et al. (1997) The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature 388:539–547

    Article  PubMed  CAS  Google Scholar 

  • Tombola F, Carlesso C, Szabó I, De Bernard M, Reyrat JM, Telford JL, Rappuoli R, Montecucco C, Papini E, Zoratti M (1999a) Helicobacter pylori vacuolating toxin forms anion-selective channels in planar lipid bilayers: possible implications for the mechanism of cellular vacuolation. Biophys J 96:1401–1409

    Article  Google Scholar 

  • Tombola F, Oregna F, Brutsche S, Szabó I, Del Giudice G, Rappuoli R, Montecucco C, Papini E, Zoratti M (1999b) Inhibition of the vacuolating and anion channel activities of the VacA toxin of Helicobacter pylori. FEBS Lett 460:221–225

    Article  PubMed  CAS  Google Scholar 

  • Tombola F, Del Giudice G, Papini E, Zoratti M (2000) Blockers of VacA provide insights into the structure of the pore. Biophys J 79:863–873

    Article  PubMed  CAS  Google Scholar 

  • van der Ende A, Pan ZJ, Bart A, van der Hulst RW, Feller M, Xiao SD, Tytgat GN, Dankert J (1998) CagA-positive Helicobacter pylori populations in China and the Netherlands are distinct. Infect Immun 66:1822–1826

    PubMed  Google Scholar 

  • Vinion-Dubiel AD, McClain MS, Czajkowsky DM, Iwamoto H, Ye D, Cao P, Schraw W, Szabó G, Blanke SR, Shao Z, Cover TL (1999) A dominant negative mutant of Helicobacter pylori vacuolating toxin (VacA) inhibits VacA-induced cell vacuolation. J Biol Chem 274:37736–37742

    Article  PubMed  CAS  Google Scholar 

  • Wandersman C (1992) Secretion across the bacterial outer membrane. Trends Genet 8:317–322

    PubMed  CAS  Google Scholar 

  • Warren JR, Marshall BJ (1983) Unidentified curved bacilli on gastric epithelium in active chronic gastritis Lancet 1:1273–1275

    Google Scholar 

  • Watts C (1997) Capture and processing of exogenous antigen for presentation on MHC molecules Annu Rev Immunol 15:821–850

    Article  PubMed  CAS  Google Scholar 

  • Weeks DL, Eskandari S, Scott DR, Sachs G (2000) A H+-gated urea channel: the link between Helicobacter pylori urease and gastric colonization. Science 287:482–485

    Article  PubMed  CAS  Google Scholar 

  • Yahiro K, Niidome T, Hatakeyama T, Aoyagi H, Kurazono H, Padilla PI, Wada A, Hirayama T (1997) Helicobacter pylori vacuolating cytotoxin binds to the 140-kDa protein in human gastric cancer cell lines, AZ-521 and AGS. Biochem Biophys Res Commun 238:629–632

    Article  PubMed  CAS  Google Scholar 

  • Yahiro K, Niidome T, Kimura M, Hatakeyama T, Aoyagi H, Kurazono H, Imagawa K, Wada A, Moss J, Hirayama T (1999) Activation of Helicobacter pylori VacA toxin by alkaline or acid conditions increases its binding to a 250-kDa receptor protein-tyrosine phosphatase. J Biol Chem 274:36693–36699

    Article  PubMed  CAS  Google Scholar 

  • Yamamura F, Yoshikawa N, Akita Y, Mitamura K, Miyasaka N (1999) Relationship between Helicobacter pylori infection and histologic features of gastritis in biopsy specimens in gastroduodenal diseases, including evaluation of diagnosis by polymerase chain reaction assay. J Gastroenterol 34:461–466

    Article  PubMed  CAS  Google Scholar 

  • Ye D, Willhite DC, Blanke SR (1999) Identification of the minimal intracellular vacuolating domain of the Helicobacter pylori vacuolating toxin. J Biol Chem 274:9277–9282

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centro CNR Biomembrane and Dipartimento di Scienze Biomediche, Università di Padova, Via G. Colombo 3, 35121, Padova, Italy

    C. Montecucco, M. De Bernard & M. Zoratti

  2. Dipartimento di Scienze Biomediche ed Oncologia Umana, Sezione di Patologia Generale, Università di Bari, 70124, Bari, Italy

    E. Papini

Authors
  1. C. Montecucco
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. De Bernard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. Papini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Zoratti
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Departement de Biochimie Sciences II, Quai Ernest-Ansermet, 1211, Genéve 4, Switzerland

    F. Gisou van der Goot

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Montecucco, C., De Bernard, M., Papini, E., Zoratti, M. (2001). Helicobacter pylori Vacuolating Cytotoxin: Cell Intoxication and Anion-Specific Channel Activity. In: van der Goot, F.G. (eds) Pore-Forming Toxins. Current Topics in Microbiology and Immunology, vol 257. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-56508-3_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-56508-3_6

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62545-9

  • Online ISBN: 978-3-642-56508-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation