Random mutagenesis of Helicobacter pylori vacA to identify amino acids essential for vacuolating cytotoxic activity

Infection and Immunity

Volumn 74, Issue 11, 2006, Pages 6188-6195

  McClain, Mark S ^a   Czajkowsky, Daniel M ^c   Torres, Victor J ^a   Szabo, Gabor ^c   Shao, Zhifeng ^c   Cover, Timothy L ^a,b  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

^c UNIVERSITY OF VIRGINIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; ARGININE; GLYCINE; LEUCINE; RECOMBINANT PROTEIN; SERINE; VACUOLATING TOXIN; VALINE;

AMINO ACID SUBSTITUTION; AMINO TERMINAL SEQUENCE; ARTICLE; BACTERIAL COLONIZATION; BACTERIAL GENE; CELL VACUOLE; CONTROLLED STUDY; CYTOTOXICITY; HELA CELL; HELICOBACTER PYLORI; HUMAN; HUMAN CELL; HYDROPHOBICITY; LIPID BILAYER; MEMBRANE CHANNEL; MEMBRANE DEPOLARIZATION; MUTAGENESIS; NONHUMAN; PEPTIC ULCER; PLASMID; POINT MUTATION; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN EXPRESSION; STOMACH CANCER; VACA GENE;

AMINO ACID SUBSTITUTION; BACTERIAL PROTEINS; CYTOTOXINS; DIMERIZATION; GLYCINE; HELA CELLS; HELICOBACTER PYLORI; HUMANS; HYDROPHOBICITY; MUTAGENESIS; SERINE; VACUOLES; VALINE;

EID: 33750485022     PISSN: 00199567     EISSN: None     Source Type: Journal    
DOI: 10.1128/IAI.00915-06     Document Type: Article

References (63)

1. Al-Awqati, Q. 1986. Proton-translocating ATPases. Annu. Rev. Cell Biol. 2:179-199.
2. Apell, H. J., and B. Bersch. 1987. Oxonol VI as an optical indicator for membrane potentials in lipid vesicles. Biochim. Biophys. Acta 903:480-494.
3. Boncristiano, M., S. R. Paccani, S. Barone, C. Ulivieri, L. Patrussi, D. Ilver, A. Amedei, M. M. D'Elios, J. L. Telford, and C. T. Baldari. 2003. The Helicobacter pylori vacuolating toxin inhibits T cell activation by two independent mechanisms. J. Exp. Med. 198:1887-1897.
4. Copass, M., G. Grandi, and R. Rappuoli. 1997. Introduction of unmarked mutations in the Helicobacter pylori vacA gene with a sucrose sensitivity marker. Infect. Immun. 65:1949-1952.
5. Cover, T. L., D. E. Berg, M. J. Blaser, and H. L. T. Mobley. 2001. H. pylori pathogenesis, p. 510-558. In E. A. Groisman (ed.), Principles of bacterial pathogenesis. Academic Press, San Diego, Calif.
6. Cover, T. L., and S. R. Blanke. 2005. Helicobacter pylori VacA, a paradigm for toxin multifunctionality. Nat. Rev. Microbiol. 3:320-332.
7. Cover, T. L., and M. J. Blaser. 1992. Purification and characterization of the vacuolating toxin from Helicobacter pylori. J. Biol. Chem. 267:10570-10575.
8. Cover, T. L., P. I. Hanson, and J. E. Heuser. 1997. Acid-induced dissociation of VacA, the Helicobacter pylori vacuolating cytotoxin, reveals its pattern of assembly. J. Cell Biol. 138:759-769.
9. Cover, T. L., W. Puryear, G. I. Pérez-Pérez, and M. J. Blaser. 1991. Effect of urease on HeLa cell vacuolation induced by Helicobacter pylori cytotoxin. Infect. Immun. 59:1264-1270.
10. Czajkowsky, D. M., H. Iwamoto, T. L. Cover, and Z. Shao. 1999. The vacuolating toxin from Helicobacter pylori forms hexameric pores in lipid bilayers at low pH. Proc. Natl. Acad. Sci. USA 96:2001-2006.
11. Czajkowsky, D. M., H. Iwamoto, G. Szabo, T. L. Cover, and Z. Shao. 2005. Mimicry of a host anion channel by a Helicobacter pylori pore-forming toxin. Biophys. J. 89:3093-3101.
12. de Bernard, M., D. Burroni, E. Papini, R. Rappuoli, J. Telford, and C. Montecucco. 1998. Identification of the Helicobacter pylori VacA toxin domain active in the cell cytosol. Infect. Immun. 66:6014-6016.
13. de Bernard, M., E. Papini, V. de Filippis, E. Gottardi, J. Telford, R. Manetti, A. Fontana, R. Rappuoli, and C. Montecucco. 1995. Low pH activates the vacuolating toxin of Helicobacter pylori, which becomes acid and pepsin resistant. J. Biol. Chem. 270:23937-23940.
14. DiRita, V. J. 1992. Co-ordinate expression of virulence genes by ToxR in Vibrio cholerae. Mol. Microbiol. 6:451-458.
15. Dunn, B. E., H. Cohen, and M. J. Blaser. 1997. Helicobacter pylori. Clin. Microbiol. Rev. 10:720-741.
16. Fischer, W., R. Buhrdorf, E. Gerland, and R. Haas. 2001. Outer membrane targeting of passenger proteins by the vacuolating cytotoxin autotransporter of Helicobacter pylori. Infect. Immun. 69:6769-6775.
17. Garner, J. A., and T. L. Cover. 1996. Binding and internalization of the Helicobacter pylori vacuolating cytotoxin by epithelial cells. Infect. Immun. 64:4197-4203.
18. Gauthier, N. C., V. Ricci, L. Landraud, and P. Boquet. 2006. Helicobacter pylori VacA toxin: a tool to study novel early endosomes. Trends Microbiol. 14:292-294.
19. Gebert, B., W. Fischer, E. Weiss, R. Hoffmann, and R. Haas. 2003. Helicobacter pylori vacuolating cytotoxin inhibits T lymphocyte activation. Science 301:1099-1102.
20. Geisse, N. A., T. L. Cover, R. M. Henderson, and J. M. Edwardson. 2004. Targeting of Helicobacter pylori vacuolating toxin to lipid raft membrane domains analysed by atomic force microscopy. Biochem. J. 381:911-917.
21. Greener, A., M. Callahan, and B. Jerpseth. 1996. An efficient random mutagenesis technique using an E. coli mutator strain. Methods Mol. Biol. 57:375-385.
22. Hille, B. 2001. Ion channels of excitable membranes, third ed. Sinauer Associates, Inc., Sunderland, Mass.
23. Iwamoto, H., D. M. Czajkowsky, T. L. Cover, G. Szabo, and Z. Shao. 1999. VacA from Helicobacter pylori: a hexameric chloride channel. FEBS Lett. 450:101-104.
24. Kim, S., A. K. Chamberlain, and J. U. Bowie. 2004. Membrane channel structure of Helicobacter pylori vacuolating toxin: role of multiple GXXXG motifs in cylindrical channels. Proc. Natl. Acad. Sci. USA 101:5988-5991.
25. Litley, D. P., and J. C. Atherton. 2000. Natural diversity in the N terminus of the mature vacuolating cytotoxin of Helicobacter pylori determines cytotoxin activity. J. Bacteriol. 182:3278-3280.
26. Letley, D. P., J. L. Rhead, R. J. Twells, B. Dove, and J. C. Atherton. 2003. Determinants of non-toxicity in the gastric pathogen Helicobacter pylori. J. Biol. Chem. 278:26734-26741.
27. Leunk, R. D., P. T. Johnson, B. C. David, W. G. Kraft, and D. R. Morgan. 1988. Cytotoxic activity in broth-culture filtrates of Campylobacter pylori. J. Med. Microbiol. 26:93-99.
28. Li, X., T. Wang, Z. Zhao, and S. A. Weinman. 2002. The ClC-3 chloride channel promotes acidification of lysosomes in CHO-K1 and Huh-7 cells. Am. J. Physiol. Cell Physiol. 282:C1483-C1491.
29. McClain, M. S., P. Cao, and T. L. Cover. 2001. Amino-terminal hydrophobic region of Helicobacter pylon vacuolating cytotoxin (VacA) mediates transmembrane protein dimerization. Infect. Immun. 69:1181-1184.
30. McClain, M. S., P. Cao, H. Iwamoto, A. D. Vinion-Dubiel, G. Szabo, Z. Shao, and T. L. Cover. 2001. A 12-amino-acid segment, present in type s2 but not type s1 Helicobacter pylori VacA proteins, abolishes cytotoxin activity and alters membrane channel formation. J. Bacteriol. 183:6499-6508.
31. McClain, M. S., and T. L. Cover. 2003. Expression of Helicobacter pylori vacuolating toxin in Escherichia coli. Infect. Immun. 71:2266-2271.
32. McClain, M. S., and T. L. Cover. 2006. Helicobacter pylori vacuolating toxin, p. 468-490. In J. E. Alouf and M. R. Popofi (ed.), The comprehensive sourcebook of bacterial protein toxins, 3rd ed. Elsevier. Amsterdam, The Netherlands.
33. McClain, M. S., H. Iwamoto, P. Cao, A. D. Vinion-Dubiel, Y. Li, G. Szabo, Z. Shao, and T. L. Cover. 2003. Essential role of a GXXXG motif for membrane channel formation by Helicobacter pylon vacuolating toxin. J. Biol. Chem. 278:12101-12108.
34. Molinari, M., C. Galli, M. de Bernard, N. Norais, J. M. Ruysschaert, R. Rappuoli, and C. Montecucco. 1998. The acid activation of Helicobacter pylori toxin VacA: structural and membrane binding studies. Biochem. Biophys. Res. Commun. 248:334-340.
35. Moll, G., E. Papini, R. Colonna, D. Burroni, J. Telford, R. Rappuoli, and C. Montecucco. 1995. Lipid interaction of the 37-kDa and 58-kDa fragments of the Helicobacter pylori cytotoxin. Eur. J. Biochem. 234:947-952.
36. Montecucco, C., and R. Rappuoli. 2001. Living dangerously: how Helicobacter pylori survives in the human stomach. Nat. Rev. Mol. Cell. Biol. 2:457-466.
37. - and water. FEBS Lett. 508:479-483.
38. Nguyen, V. Q., R. M. Caprioli, and T. L. Cover. 2001. Carboxy-terminal proteolytic processing of Helicobacter pylori vacuolating toxin. Infect. Immun. 69:543-546.
39. Reyrat, J. M., S. Lanzavecchia, P. Lupetti, M. de Bernard, C. Pagliaccia, V. Pelicic, M. Charrel, C. Ulivieri, N. Norais, X. Ji, V. Cabiaux, E. Papini, R. Rappuoli, and J. L. Telford. 1999. 3D imaging of the 58 kDa cell binding subunit of the Helicobacter pylori cytotoxin. J. Mol. Biol. 290:459-470.
40. Russ, W. P., and D. M. Engelman. 2000. The GxxxG motif, a framework for transmembrane helix-helix association. J. Mol. Biol. 296:911-919.
41. Russ, W. P., and D. M. Engelman. 1999. TOXCAT: a measure of transmembrane helix association in a biological membrane. Proc. Natl. Acad. Sci. USA 96:863-868.
42. Salama, N. R., G. Otto, L. Tompkins, and S. Falkow. 2001. Vacuolating cytotoxin of Helicobacter pylon plays a role during colonization in a mouse model of infection. Infect. Immun. 69:730-736.
43. Schraw, W., Y. Li, M. S. McClain, F. G. van der Goot, and T. L. Cover. 2002. Association of Helicobacter pylori vacuolating toxin (VacA) with lipid rafts. J. Biol. Chem. 277:34642-34650.
44. Seto, K., Y. Hayashi-Kuwabara, T. Yoneta, H. Suda, and H. Tamaki. 1998. Vacuolation induced by cytotoxin from Helicobacter pylori is mediated by the EGF receptor in HeLa cells. FEBS Lett. 431:347-350.
45. Suerbaum, S., and P. Michetti. 2002. Helicobacter pylori infection. N. Engl. J. Med. 347:1175-1186.
46. Sundrud, M. S., V. J. Torres, D. Unutmaz, and T. L. Cover. 2004. Inhibition of primary human T cell proliferation by Helicobacter pylori vacuolating toxin (VacA) is independent of VacA effects on IL-2 secretion. Proc. Natl. Acad. Sci. USA 101:7727-7732.
47. Szabo, I., S. Brutsche, F. Tombola, M. Moschioni, B. Satin, J. L. Telford, R. Rappuoli, C. Montecucco, E. Papini, and M. Zoratti. 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.
48. Telford, J. L., P. Ghiara, M. Dell'Orco, M. Comanducci, D. Burroni, M. Bugnoli, M. F. Tecce, S. Censini, A. Covacci, Z. Xiang, E. Papini, C. Montecucco, L. Parente, and R. Rappuoli. 1994. Gene structure of the Helicobacter pylori cytotoxin and evidence of its key role in gastric disease. J. Exp. Med. 179:1653-1658.
49. Tombola, F., C. Carlesso, I. Szabo, M. de Bernard, J. M. Reyrat, J. L. Telford, R. Rappuoli, C. Montecucco, E. Papini, and M. Zoratti. 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.
50. Torres, V. J., S. E. Ivie, M. S. McClain, and T. L. Cover. 2005. Functional properties of the p33 and p55 domains of the Helicobacter pylori vacuolating cytotoxin. J. Biol. Chem. 280:21107-21114.
51. Torres, V. J., M. S. McClain, and T. L. Cover. 2004. Interactions between p-33 and p-55 domains of the Helicobacter pylon vacuolating cytotoxin (VacA). J. Biol. Chem. 279:2324-2331.
52. Torres, V. J., M. S. McClain, and T. L. Cover. 2006. Mapping of a domain required for protein-protein interactions and inhibitory activity of a Helicobacter pylori dominant-negative VacA mutant protein. Infect. Immun. 74:2093-2101.
53. Utt, M., B. Danielsson, and T. Wadstrom. 2001. Helicobacter pylori vacuolating cytotoxin binding to a putative cell surface receptor, heparan sulfate, studied by surface plasmon resonance. FEMS Immunol. Med. Microbiol. 30:109-113.
54. Vinion-Dubiel, A. D., M. S. McClain, P. Cao, R. L. Mernaugh, and T. L. Cover. 2001. Antigenic diversity among Helicobacter pylori vacuolating toxins. Infect. Immun. 69:4329-4336.
55. Vinion-Dubiel, A. D., M. S. McClain, D. M. Czajkowsky, H. Iwamoto, D. Ye, P. Cao, W. Schraw, G. Szabo, S. R. Blanke, Z. Shao, and T. L. Cover. 1999. A dominant negative mutant of Helicobacter pylori vacuolating toxin (VacA) inhibits VacA-induced cell vacuolation. J. Biol. Chem. 274:37736-37742.
56. Wang, H. J., and W. C. Wang. 2000. Expression and binding analysis of GST-vac4 fusions reveals that the C-terminal approximately 100-residue segment of exotoxin is crucial for binding in HeLa cells. Biochem. Biophys. Res. Commun. 278:449-454.
57. Willhite, D. C., T. L. Cover, and S. R. Blanke. 2003. Cellular vacuolation and mitochondrial cytochrome c release are independent outcomes of Helicobacter pylori vacuolating cytotoxin activity that are each dependent on membrane channel formation. J. Biol. Chem. 278:48204-48209.
58. Yahiro, K., T. Niidome, T. Hatakeyama, H. Aoyagi, H. Kurazono, P. I. Padilla, A. Wada, and T. Hirayama. 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.
59. Yahiro, K., T. Niidome, M. Kimura, T. Hatakeyama, H. Aoyagi, H. Kurazono, K. Imagawa, A. Wada, J. Moss, and T. Hirayama. 1999. Activation of Helicobacter pylori VacA toxin by alkaline or acid conditions increases its binding to a 250-kDa receptor protein-tyrosine phosphatase beta. J. Biol. Chem. 274:36693-36699.
60. Yahiro, K., A. Wada, M. Nakayama, T. Kimura, K. Ogushi, T. Niidome, H. Aoyagi, K. Yoshino, K. Yonezawa, J. Moss, and T. Hirayama. 2003. Protein-tyrosine phosphatase alpha, RPTP alpha, is a Helicobacter pylori VacA receptor. J. Biol. Chem. 278:19183-19189.
61. Ye, D., and S. R. Blanke. 2002. Functional complementation reveals the importance of intermolecular monomer interactions for Helicobacter pylori VacA vacuolating activity. Mol. Microbiol. 43:1243-1253.
62. Ye, D., and S. R. Blanke. 2000. Mutational analysis of the Helicobacter pylori vacuolating toxin amino terminus: identification of amino acids essential for cellular vacuolation. Infect. Immun. 68:4354-4357.
63. Ye, D., D. C. Willhite, and S. R. Blanke. 1999. Identification of the minimal intracellular vacuolating domain of the Helicobacter pylori vacuolating toxin. J. Biol. Chem. 274:9277-9282.