Formation of anion-selective channels in the cell plasma membrane by the toxin VacA of Helicobacter pylori is required for its biological activity

EMBO Journal

Volumn 18, Issue 20, 1999, Pages 5517-5527

  Szabò, Ildikò ^a   Brutsche, Sandra ^a,b   Tombola, Francesco ^a   Moschioni, Monica ^a   Satin, Barbara ^a   Telford, John L ^c   Rappuoli, Rino ^c   Montecucco, Cesare ^a   Papini, Emanuele ^d   Zoratti, Mario ^a  

^a UNIVERSITY OF PADOVA   (Italy)

^b SANOFI   (France)

^c CHIRON VACCINES   (Italy)

^d UNIVERSITY OF BARI   (Italy)

Author keywords

Anion channel; Epithelial permeability; Helicobacter pylori; VacA; Vacuolation

Indexed keywords

(2 CYCLOPENTYL 6,7 DICHLORO 2 METHYL 1 OXO 5 INDANYLOXY)ACETIC ACID; 5 NITRO 2 (3 PHENYLPROPYLAMINO)BENZOIC ACID; ANION CHANNEL; BACTERIAL TOXIN; CALCIUM ION; CHLORIDE CHANNEL; CHLORIDE CHANNEL BLOCKING AGENT;

ANIMAL CELL; ARTICLE; CELL MEMBRANE; CELL MEMBRANE PERMEABILITY; CELL VACUOLE; CONTROLLED STUDY; ELECTROPHYSIOLOGY; HELA CELL; HELICOBACTER PYLORI; HUMAN; HUMAN CELL; LIPID BILAYER; MEMBRANE CHANNEL; MEMBRANE CONDUCTANCE; NONHUMAN; PRIORITY JOURNAL;

ANIMALS; BACTERIAL PROTEINS; BACTERIAL TOXINS; CELL LINE; CELL MEMBRANE; CELL MEMBRANE PERMEABILITY; CHLORIDE CHANNELS; DOGS; GLYCOLATES; HELA CELLS; HELICOBACTER PYLORI; HUMANS; ION CHANNELS; LIPID BILAYERS; MEMBRANE POTENTIALS; NITROBENZOATES; VACUOLES; VIRULENCE;

EID: 13044317274     PISSN: 02614189     EISSN: None     Source Type: Journal    
DOI: 10.1093/emboj/18.20.5517     Document Type: Article

References (62)

1. Anderson, M.P., Rich, D.P., Gregory, R.J., Smith, A.E. and Welsh, M.J. (1991) Generation of cAMP-activated chloride current by expression of CFTR. Science, 251, 679-682.
2. Apell, H.J. and Bersch, B. (1987) Oxonol VI as an optical indicator for membrane potentials in lipid vesicles. Biochim. Biophys. Acta, 903, 480-494.
3. Barasch, J., Kiss, B., Prince, A., Saiman, L., Gruenert, D. and al-Awqati, Q. (1991) Defective acidification of intracellular organelles in cystic fibrosis. Nature, 352, 70-73.
4. Biwersi, J. and Verkman, A.S. (1994) Functional CFTR in endosomal compartment of CFTR-expressing fibroblasts and T84 cells. Am. J. Physiol., 266, C149-C156.
5. Biwersi, J., Emans, N. and Verkman, A.S. (1996) Cystic fibrosis transmembrane conductance regulator activation stimulates endosome fusion in vivo. Proc. Natl Acad. Sci. USA, 93, 12484-12489.
6. Blaser, M.J. (1993) Helicobacter pylori: microbiology of a 'slow' bacterial infection. Trends Microbiol., 1, 255-259.
7. Bradbury, N.A. (1999) Intracellular CFTR: localization and function. Physiol. Rev., 79, S175-S191.
8. 2 for growth. Microbiology, 141, 3113-3118.
9. 3- exchange? J. Physiol., 499, 763-71.
10. Cover, T.L. (1997) The vacuolating cytotoxin of Helicobacter pylori. Mol. Microbiol., 20, 241-246.
11. Cover, T.L. and Blaser, M.J. (1992) Purification and characterization of the vacuolating toxin from Helicobacter pylori. J. Biol. Chem., 267, 10570-10575.
12. Cover, T.L., Cao, P., Lind, C.D., Tham, K.T. and Blaser, M.J. (1993a) Correlation between vacuolating cytotoxin production by Helicobacter pylori isolates in vitro and in vivo. Infect. Immun., 61, 5008-5012.
13. Cover, T.L., Reddy, L.Y. and Blaser, M.J. (1993b) Effects of ATPase inhibitors on lhe response of HeLa cells to Helicobacter pylori vacuolating toxin. Infect. Immun., 61, 1427-1431.
14. Cover, T.L., Tummuru, M.K.R., Cao, P., Thompson, S.A. and Blaser, M.J. (1994) Divergence of genetic sequences for the vacuolating cytotoxin among Helicobacter pylori strains. J. Biol. Chem., 269, 10566-10573.
15. Cover, T.L., Hanson, P.I. and Heuser, J.E. (1997) Acid-induced dissociation of VacA, the Helicobacter pylori vacuolating toxin, reveals its pattern of assembly. J. Cell Biol., 138, 759-769.
16. Czajkowsky, D.M., Iwamoto, H., Cover, T.L. and 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.
17. Debellis, L., Caroppo, R., Fromter, E. and Curci, S. (1998) Alkaline secretion by frog gastric glands measured with pH microelectrodes in the gland lumen. J. Physiol. (London), 513, 235-241.
18. de Bernard, M., Papini, E., de Filippis, V., Gottardi, E., Telford., J., Manetti, R., Fontana, A., Rappuoli, R. and Montecucco, C. (1995) Low pH activates the vacuolating toxin of Helicobacter pylori, which becomes acid and pepsin resistant. J. Biol. Chem., 270, 23937-23940.
19. de Bernard, M., Aricò, B., Papini, E., Rizzuto, R., Grandi, G., Rappuoli, R. and Montecucco, C. (1997) Helicobacter pylori toxin VacA induces vacuole formation by acting in the cell cytosol. Mol. Microbiol., 26, 665-674.
20. de Bernard, M., Burroni, D., Papini, E., Rappuoli, R., Telford, J.L. and Montecucco, C. (1998a) Identification of the Helicobacter pylori VacA toxin domain active in the cell cytosol. Infect. Immun., 66, 6014-6016.
21. de Bernard, M., Moschioni, M., Papini, E., Telford, J.L., Rappuoli, R. and Montecucco, C. (1998b) Cell vacuolization induced by Helicobacter pylori VacA toxin: cell line sensitivity and quantitative extimation. Toxicol. Lett., 99, 109-115.
22. Dunn, K.W, Park, J., Semrad, C.E., Gelman, D.L., Shevell, T. and McGraw, T.E. (1994) Regulation of endocytic trafficking and acidification are independent of the cystic fibrosis transmembrane regulator. J. Biol. Chem., 269, 5336-5345.
23. Fuerst, T.R., Niles, E.G., Studier, F.W. and Moss, B. (1986) Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesises bacteriophage T7 RNA polymerase. Proc. Natl Acad. Sci. USA, 83, 8122-8126.
24. Galloway, C.J., Dean, G.E., Marsh, M., Rudnick, G. and Mellman, I. (1983) Acidification of macrophage and fibroblast endocytic vesicles in vitro. Proc. Natl Acad. Sci. USA, 80, 3334-3338.
25. Garner, J.A. and Cover, T.L. (1996) Binding and internalization of Helicobacter pylori vacuolating cytotoxin by epithelial cells. Infect. Immun., 64, 4197-4203.
26. Guarino, A., Bisceglia, M., Canani, R.B., Boccia, M.C., Mallardo, G., Bruzzese, E., Massari, P., Rappuoli, R. and Telford, J. (1998) Enterotoxic effect of the vacuolating toxin produced by Helicobacter pylori in Caco-2 cells. J. Infect. Dis., 178, 1373-1378.
27. +-medium. Biochim. Biophys. Acta, 1068, 87-96.
28. Iwamoto, H., Czajkowsky, D.M., Cover, T.L., Szabo, G. and Shao, Z. (1999) VacA from Helicobacter pylori: a hexameric chloride channel. FEBS Lett., 450, 101-104.
29. Kimura, M., Goto, S., Wada, A., Yahiro, K., Niidome, T., Hatakeyama, T., Aoyagi, H., Hirayama, T. and Kondo, T. (1999) Vacuolating cytotoxin purified from Helicobacter pylori causes mitochondrial damage in human gastric cells. Microb. Pathog., 26, 45-52.
30. Lang, F., Busch, G.L., Ritter, M., Völkl, H., Waldegger, S., Gulbins, E. and Häussinger, D. (1998) Functional significance of cell volume regulatory mechanisms. Physiol. Rev., 78, 247-306.
31. Lanzavecchia, S., Bellon, P.L., Lupetti, P., Dallai, R., Rappuoli, R. and Telford, J.L. (1998) Three-dimensional reconstruction of metal replicas of the Helicobacter pylori vacuolating cytotoxin. J. Struct. Biol., 121, 9-18.
32. Leunk, R.D., Johnson, P.T., David, B.C., Kraft, W.G. and Morgan, D.R. (1988) Cytotoxin activity in broth-culture filtrates of Campylobacter pylori. J. Med. Microbiol., 26, 93-99.
33. Lepple-Wienhues, A., Szabò, I., Laun, T., Kaba, N.K., Gulbins, E. and Lang, F. (1998) The tyrosine kinase p56lck mediates activation of swelling-induced chloride channels in lymphocytes. J. Cell Biol., 141, 281-286.
34. Lukacs, G.L, Chang, X.B., Kartner, N., Rotstein, O.D., Riordan, J.R. and Grinstein, S. (1992) The cystic fibrosis transmembrane regulator is present and functional in endosomes. Role as a determinant of endosomal pH. J. Biol. Chem., 267, 14568-14572.
35. Lupetti, P., Heuser, J.E., Manetti, R., Lanzavecchia, S., Bellon, P.L., Dallai, R., Rappuoli, R. and Telford, J.L. (1996) Oligomeric and subunit structure of the Helicobacter pylori vacuolating cytotoxin. J. Cell Biol., 133, 801-807.
36. Manetti, R. et al. (1995) Helicobacter pylori cytotoxin: importance of native conformation for induction of neutralizing antibodies. Infect. Immun., 63, 4476-4480.
37. Marchetti, M., Aricò, B., Burroni, D., Figura, N., Rappuoli, R. and Ghiara, P. (1995) Development of a mouse model of Helicobacter pylori infection that mimics human disease. Science, 265, 1656-1658.
38. Mendz, G.L., Hazell, S.L. and van Gorkom, L. (1994) Pyruvate metabolism in Helicobacter pylori. Arch. Microbiol., 162, 187-192.
39. Menestrina, G., Schiavo, G. and Montecucco, C. (1994) Molecular mechanisms of action of bacterial protein toxins. Mol. Aspects Med., 15, 79-193.
40. Molinari, M., Galli, C., Norais, N., Telford, J.L., Rappuoli, R., Luzio, J.P. and Montecucco, C. (1997) Vacuoles induced by Helicobacter pylori toxin contain both late endosomal and lysosomal markers. J. Biol. Chem., 272, 25339-25344.
41. Moll, G., Papini, E., Colonna, R., Burroni, D., Telford, J.L., Rappuoli, R. and Montecucco, C. (1995) Lipid interaction of the 37-kDa and 58-kDa fragments of the Helicobacter pylori cytotoxin. Eur. J. Biochem., 234, 947-952.
42. Montecucco, C. (1998) Protein toxins and membrane transport. Curr. Opin. Cell Biol., 10, 530-536.
43. Montecucco, C., Papini, E. and Schiavo, G. (1994) Bacterial protein toxins penetrate cells via a four-step mechanism. FEBS Lett., 346, 92-98.
44. Nilius, B., Prenen, J., Szucs, G., Wei, L., Tanzi, F., Voets, T. and Droogmans, G. (1997a) Calcium-activated chloride channels in bovine pulmonary artery endothelial cells. J. Physiol., 498, 381-396.
45. Nilius, B., Prenen, J., Voets, T., VanDen Bremt, K., Eggermont, J. and Droogmans, G. (1997b) Kinetic and pharmacological properties of the calcium-activated chloride-current in macrovascular endothelial cells. Cell Calcium, 22, 53-63.
46. Papini, E., Bugnoli, M., de Bernard, M., Figura, N., Rappuoli, R. and Montecucco, C. (1993) Bafilomycin A1 inhibits Helicobacter pylori-induced vacuolization of HeLa cells. Mol. Microbiol., 7, 323-327.
47. Papini, E., de Bernard, M., Milia, E., Zerial, M., Rappuoli, R. and Montecucco, C. (1994) Cellular vacuoles induced by Helicobacter pylori originate from late endosomal compartments. Proc. Natl Acad. Sci. USA, 9117, 9720-9724.
48. Papini, E., Gottardi, E., Satin, B., de Bernard, M., Telford, J., Massari, P., Rappuoli, R., Sato, S.B. and Montecucco, C. (1996) The vacuolar ATPase proton pump on intracellular vacuoles induced by Helicobacter pylori. J. Med. Microbiol., 44, 1-6.
49. Papini, E., Satin, B., Bucci, C., de Bernard, M., Telford, J.L., Manetti, R., Rappuoli, R., Zerial, M. and Montecucco, C. (1997) The small GTP binding protein rab7 is essential for cellular vacuolation induced by Helicobacter pylori cytotoxin. EMBO J., 16, 15-24.
50. Papini, E., Satin, B., Norais, N., de Bernard, M., Telford, J.L., Rappuoli, R. and Montecucco, C. (1998) Selective increase of the permeability of polarized epithelial cell monolayers by Helicobacter pylori vacuolating toxin. J. Clin. Invest., 102, 813-20.
51. Pelicic, V., Reyrat, J.M., Sartori, L., Pagliaccia, C., Rappuoli, R., Telford, J.L., Montecucco, C. and Papini, E. (1999) Helicobacter pylori VacA cytotoxin associated to the bacteria increases epithelial permeability independently of its vacuolating activity. Microbiology, 145, 2043-2050.
52. Reyrat, J.M. et al. (1999) 3D imaging of the 58 kDa cell binding subunit of the Helicobacter pylori cytotoxin. J. Mol. Biol., 290, 459-470.
53. Ricci, V., Sommi, P., Fiocca, R., Romano, M., Solcia, E. and 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.
54. Sommi, P., Ricci, V., Fiocca, R., Necchi, V., Romano, M., Telford, J.L., Solcia, E. and Ventura, U. (1998) Persistence of Helicobacter pylori VacA toxin and vacuolating potential in cultured gastric cells. Am. J. Physiol., 275, 0681-688.
55. Stein, M.A., Mathers, D.A., Yan, H., Baimbridge, K.G. and Finley, B.B. (1996) Enteropathogenic Escherichia coli markedly decreases the resting membrane potential of CaCo2 and HeLa human epithelial cells. Infect. Immun., 64, 4820-4825.
56. Telford, J.L. et al. (1994) Purification and characterization of the vacuolating toxin from Helicobacter pylori. J. Exp. Med., 179, 1653-1658.
57. Tombola, F. et al. (1999) Helicobacter pylori vacuolating toxin forms anion-selective channels in planar lipid bilayers: possible implications for the mechanism of cellular vacuolation. Biophys. J., 76, 1401-1409.
58. Van Dyke, R.W. (1986) Anion inhibition of the proton pump in rat liver multivesicular bodies. J. Biol. Chem., 261, 15941-15948.
59. Vennekens, R., Trouet, D., Vankeerberghen, A., Voets, T., Cuppens, H., Eggermont, J., Cassiman, J.-J., Droogmans, G. and Nilius, B. (1999) Inhibition of volume-regulated anion channels by expression of the cystic fibrosis transmembrane conductance regulator. J. Physiol., 515, 75-85.
60. Ye, D., Willhite, D.C. and Blanke, S.R. (1999) Identification of the minimal intracellular vacuolating domain of the Helicobacter pylori vacuolating toxin. J. Biol. Chem., 274, 9277-9282.
61. Xiang, Z., Censini, S., Bayeli, P.F., Telford, J.L., Figura, N., Rappuoli, R. and Covacci, A. (1995) Analysis of expression of CagA and VacA virulence factors in 43 strains of Helicobacter pylori reveals that clinical isolates can be divided into two major types and that CagA is not necessary for expression of the vacuolating cytotoxin. Infect. Immun., 63, 94-98.
62. Zhang, W., Mannan, I., Schulz, S., Parkinson, S.J., Alekseev, A.E., Gomez, L.A., Terzic, A. and Waldman, S.A. (1999) Interruption of transmembrane signalling as a novel antisecretory strategy to treat enterotoxigenic diarrhea. FASEB J., 13, 913-922.