Ion Metabolism and Transport

Arnoud H. M. van Vliet; Johannes G. Kusters; Stefan Bereswill

doi:10.1128/9781555818005.ch17

Chapter 17 : Ion Metabolism and Transport

Authors: Arnoud H. M. van Vliet¹, Johannes G. Kusters¹, Stefan Bereswill³

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Affiliations: 1: Department of Medical Microbiology, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands; 2: Present address: Department of Gastroenterology and Hepatology, Academic Hospital Dijkzigt, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands; 3: Department of Microbiology, Institute of Medical Microbiology and Hygiene, University of Freiburg, Hermann-Herder-Str. 11, D-79104 Freiburg, Germany

Content Type: Monograph

Publication Year: 2001

Category: Bacterial Pathogenesis

Book DOI: 10.1128/9781555818005

Chapter DOI: 10.1128/9781555818005.ch17

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Abstract:

This chapter concentrates on the mechanisms used by Helicobacter pylori to maintain its ion homeostasis, emphasizing metal cations. Maintaining ion homeostasis requires both sensor systems to detect the cytoplasmic ion concentration and effector systems to restore normal cell conditions, or to cope with stress caused by ion imbalance. Iron availability is usually low in most environments, and thus bacteria require specific high-affinity iron acquisition systems. The adaptation of H. pylori to life in the gastric mucosa seems to have led to a more pronounced role of nickel in its metabolism, for example, in its role as an essential cofactor of urease, which mediates acid resistance of H. pylori. Urease plays a central role in the pathogenesis of H. pylori infection and catalyzes the conversion of urea into carbon dioxide and ammonia. The latter is able to neutralize gastric acid and offer protection to H. pylori against the low pH in the stomach. Concerning competition for nutrients as well as the acidic pH, the niche differs considerably from the environments most other bacteria colonize. Elements of its systems for ion metabolism and transport seem to reflect specific adaptations of H. pylori to its ecological niche, and the functions and mechanisms involved might be different from the paradigms developed for enteric bacteria like Escherichia coli. H. pylori contains relatively low numbers of ion transport systems, except for nickel and iron. These two ions can be transported by two or more systems, indicating their importance in the physiology of H. pylori.

Citation: van Vliet A, Kusters J, Bereswill S. 2001. Ion Metabolism and Transport, p 193-206. In Mobley H, Mendz G, Hazell S (ed), Helicobacter pylori. ASM Press, Washington, DC. doi: 10.1128/9781555818005.ch17

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Ion Metabolism and Transport

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Figure 1

Schematic representation of the mechanisms involved in maintaining ion homeostasis.

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Figure 1

Schematic representation of the mechanisms involved in maintaining ion homeostasis.

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Figure 2

Schematic overview of ion transport systems of H. pylori. The ion transported and the direction of transport are indicated. OM, outer membrane; CM, cytoplasmic membrane. Ion transporters are grouped depending on the direction of transport: importers at the top, and exporters at the bottom.

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Figure 2

References

/content/book/10.1128/9781555818005.chap17

1. Alm, R. A.,, L. S. Ling,, D. T. Moir,, B. L. King,, E. D. Brown,, P. C. Doig,, D. R. Smith,, B. Noonan,, B. C. Guild,, B. L. de Jonge,, G. Carmel,, P. J. Tummino,, A. Caruso,, M. Uria-Nickelsen,, D. M. Mills,, C. Ives,, R. Gibson,, D. Merberg,, S. D. Mills,, Q. Jiang,, D. E. Taylor,, G. F. Vovis,, and T. J. Trust. 1999. Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature 397: 176– 180.

2. Andrews, S. C. 1998. Iron storage in bacteria. Adv. Microb. Physiol. 40: 281– 351.

3. Bauerfeind, P.,, R. Garner,, B. E. Dunn,, and H. L. Mobley. 1997. Synthesis and activity of Helicobacter pylori urease and catalase at low pH. Gut 40: 25– 30.

4. Bauerfeind, P.,, R. M. Garner,, and L. T. Mobley. 1996. Allelic exchange mutagenesis of nixA in Helicobacter pylori results in reduced nickel transport and urease activity. Infect. Immun. 64: 2877– 2880.

5. Bayle, D.,, S. Wangler,, T. Weitzenegger,, W. Steinhilber,, J. Volz,, M. Przybylski,, K. P. Schafer,, G. Sachs,, and K. Melchers. 1998. Properties of the P-type ATPases encoded by the copAP operons of Helicobacter pylori and Helicobacter felis.J. Bacteriol. 180: 317– 329.

6. Beier, D.,, G. Spohn,, R. Rappuoli,, and V. Scarlato. 1997. Identification and characterization of an operon of Helicobacter pylori that is involved in motility and stress adaptation. J. Bacterial. 179: 4676– 4683.

7. Bereswill, S.,, F. Fassbinder,, C. Volzing,, A. Covacci,, R. Haas,, and M. Kist. 1998. Hemolytic properties and riboflavin synthesis of Helicobacter pylori: cloning and functional characterization of the ribA gene encoding GTP-cyclohydrolase II that confers hemolytic activity to Escherichia coli. Med. Microbiol. Immunol. 186: 177– 187.

8. Bereswill, S.,, F. Fassbinder,, C. Volzing,, R. Haas,, K. Reuter,, R., Ficner,, and M. Kist. 1997. Cloning and functional characterization of the genes encoding 3-dehydroquinate synthase ( aroB) and tRNA-guanine transglycosylase ( tgt) from Helicobacter pylori. Med. Microbiol. Immunol. 186: 125– 134.

9. Bereswill, S.,, S. Greiner,, A. H. M. van Vliet,, B. Waidner,, F. Fassbinder,, E. Schiltz,, J. G. Kusters,, and M. Kist. 2000. Regulation of ferritin-mediated cytoplasmic iron storage by the ferric uptake regulator homolog (Fur) of Helicobacter pylori. J. Bacteriol. 182: 5948– 5953.

10. Bereswill, S.,, S. Greiner,, J. Velayndhan,, D. J. Kelly,, and M. Kist. 1999. Iron-dependent regulation of the Helicobacter pylori ferritin gene pfr and the role of ferritin in metal-resistance. Gut 45( S3): A9.

11. Bereswill, S.,, F. Lichte,, T. Vey,, F. Fassbinder,, and M. Kist. 1998. Cloning and characterization of the fur gene from Helicobacter pylori. FEMS Microbiol. Lett. 159: 193– 200.

12. Bereswill, S.,, O. Neuner,, S. Strobel,, and M. Kist. 2000. Identification and molecular analysis of superoxide dismutase iso-forms in Helicobacter pylori. FEMS Microbiol. Lett. 183: 241– 245.

13. Bereswill, S.,, S. Strobel,, F. Lichte,, F. Fassbinder,, K. Hantke,, and M. Kist. 1997. Evaluation of microbiological parameters for the study of iron metabolism in Helicobacter pylori. Gut 41( S1): A10.

14. Bereswill, S.,, U. Waidner,, S. Odenbreit,, F. Lichte,, F. Fassbinder,, G. Bode,, and M. Kist. 1998. Structural, functional and mutational analysis of the pfr gene encoding a ferritin from Helicobacter pylori. Microbiology 144: 2505– 2516.

15. Berg, D. E.,, P. S. Hoffman,, B. J. Appelmelk,, and J. G. Kusters. 1997. The Helicobacter pylori genome sequence: genetic factors for long life in the gastric mucosa. Trends Microbiol. 5: 468– 474.

16. Biegel Carson, S. D.,, P. E. Klebba,, S. M. C. Newton,, and P. F. Sparling. 1999. Ferric enterobactin binding and utilization by Neisseria gonorrhoeae. J. Bacteriol. 181: 2895– 2901.

17. Bijlsma, J. J. E.,, S. Bereswill,, A. H. M. van Vliet,, C. M. J. E. Vandenbroucke-Grauls,, M. Kist,, and J. G. Kusters. 1999. The Fur homologue of Helicobacter pylori is involved in acid-resistance. Gut 45( S3): A25.

18. Bijlsma, J. J. E.,, M. Lie-a-Ling,, I. C. Nooteboom,, C. M. J. E. Vandenbroucke-Grauls,, and J. G. Kusters. 2000. Identification of loci essential for the growth of Helicobacter pylori under acidic conditions. J. Infect. Dis 182: 1566– 1569.

19. Bozzi, M.,, G. Mignogna,, S. Stefanini,, D. Barra,, C. Longhi,, P. Valenti,, and E. Chiancone. 1997. A novel non-heme iron-binding ferritin related to the DNA-binding proteins of the Dps family in Listeria innocua. J. Biol. Chem. 272: 3259– 3265.

20. Braun, V.,, K. Hantke,, and W. Koster. 1998. Bacterial iron transport: mechanisms, genetics, and regulation. Metal Ions Biol. Syst. 35: 67– 145.

21. Braun, V.,, and H. Killmann. 1999. Bacterial solutions to the iron-supply problem. Trends Biochem. Sci. 24: 104– 109.

22. Chan, E. C.,, C. C. Chang,, Y. S. Li,, C. A. Chang,, C. C. Chiou,, and T. Z. Wu. 2000. Purification and characterization of neutral sphingomyelinase from Helicobacter pylori. Biochemistry 39: 4838– 4845.

23. Chivers, P. T.,, and R. T. Sauer. 1999. NikR is a ribbon-helix-helix DNA-binding protein. Protein Sci. 8: 2494– 2500.

24. Chivers, P. T.,, and R. T. Sauer. 2000. Regulation of high-affinity nickel uptake in bacteria: Ni 2+-dependent interaction of NikR with wild-type and mutant operator sites. J. Biol. Chem. 275: 19735– 19741.

25. Christensen, J. M.,, J. Kristiansen,, N. H. Nielsen,, T. Menne,, and K. Byrialsen. 1999. Nickel concentrations in serum and urine of patients with nickel eczema. Toxicol. Lett. 108: 185– 189.

26. Cobine, P.,, W. A. Wickramasinghe,, M. D. Harrison,, T. Weber,, M. Solioz,, and C. T. Dameron. 1999. The Enterococcus hirae copper chaperone CopZ delivers copper(I) to the CopY repressor. FEBS Lett. 445: 27– 30.

27. Contreras, M.,, M. A. Mandrand-Berthelot,, and A. Labigne. 1999. Identification and characterization in H. pylori of NikR, an homologue of a nickel-responsive regulator in E. coli, abstr. HG18, p. 135. In Abstr. 10th Int. Workshop Campylobacter, Helicobacter and Related Organisms. University of Maryland, Baltimore.

28. Csonka, L. N.,, and W. Epstein,. 1996. Osmoregulation, p. 1210– 1223. In F. C. Neidhardt (ed.), Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd ed. ASM Press, Washington, D.C.

29. Cussac, V.,, R. L. Ferrero,, and A. Labigne. 1992. Expression of Helicobacter pylori urease genes in Escherichia coli grown under nitrogen-limiting conditions. J. Bacteriol. 174: 2466– 2473.

30. De Pina, K.,, V. Desjardin,, M. A. Mandrand-Berthelot,, G. Giordano,, and L. F. Wu. 1999. Isolation and characterization of the nikR gene encoding a nickel-responsive regulator in Escherichia coli. J. Bacteriol. 181: 670– 674.

31. Dhaenens, L.,, F. Szczebara,, and M. O. Husson. 1997. Identification, characterization, and immunogenicity of the lacto-ferrin-binding protein from Helicobacter pylori. Infect. Immun. 65: 514– 518.

32. Dhaenens, L.,, F. Szczebara,, S. Van Nieuwenhuyse,, and M. O. Husson. 1999. Comparison of iron uptake in different Helicobacter species. Res. Microbiol. 150: 475– 481.

33. Doig, P.,, J. W. Austin,, and T. J. Trust. 1993. The Helicobacter pylori 19.6-kilodalton protein is an iron-containing protein resembling ferritin. J. Bacteriol. 175: 557– 560.

34. Dubrac, S.,, and D. Touati. 2000. Fur positive regulation of iron superoxide dismutase in Escherichia coli: functional analysis of the sodB promoter. J. Bacteriol. 182: 3802– 3808.

35. Dunn, B. E.,, G. P. Campbell,, G. I. Perez-Perez,, and M. J. Blaser. 1990. Purification and characterization of urease from Helicobacter pylori. J. Biol. Chem. 265: 9464– 9469.

36. Earhart, C. F., 1996. Uptake and metabolism of iron and molybdenum, p. 1075– 1090. In F. C. Neidhardt (ed.), Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd ed. ASM Press, Washington, D.C.

37. Eitinger, T.,, and M. A. Mandrand-Berthelot. 2000. Nickel transport systems in microorganisms. Arch. Microbiol. 173: 1– 9.

38. Escolar, L.,, J. Perez-Martin,, and V. de Lorenzo. 1999. Opening the iron-box: transcriptional metalloregulation by the Fur protein. J. Bacteriol. 181: 6223– 6229.

39. Evans, D. J., Jr.,, D. G. Evans,, T. Takemura,, H. Nakano,, H. C. Lampert,, D. Y. Graham,, D. N. Granger,, and P. R. Kvietys. 1995. Characterization of a Helicobacter pylori neutrophil-activating protein. Infect. Immun. 63: 2213– 2220.

40. Fassbinder, F.,, A. H. M. van Vliet,, V. Gimmel,, J. G. Kusters,, M. Kist,, and S. Bereswill. 2000. Identification of iron-regulated genes of Helicobacter pylori by a modified Fur titration assay (FURTA-Hp). FEMS Microbiol Lett. 184: 225– 229.

41. Frazier, B. A.,, J. D. Pfeifer,, D. G. Russell,, P. Falk,, A. N. Olsen,, M. Hammar,, T. U. Westblom,, and S. J. Normark. 1993. Paracrystalline inclusions of a novel ferritin containing nonheme iron, produced by the human gastric pathogen Helicobacter pylori: evidence for a third class of ferritins. J. Bacteriol. 175: 966– 972.

42. Fulkerson, J. F.,, R. M. Garner,, and H. L. Mobley. 1998. Conserved residues and motifs in the NixA protein of Helicobacter pylori are critical for the high affinity transport of nickel ions. J. Biol. Chem. 273: 235– 241.

43. Fulkerson, J. F.,, and H. L. Mobley. 2000. Membrane topology of the NixA nickel transporter of Helicobacter pylori: two nickel transport-specific motifs within transmembrane helices II and III. J. Bacteriol. 182: 1722– 1730.

44. Garcia Vescovi, E.,, F. C. Soncini,, and E. A. Groisman. 1996. Mg 2+ as an extracellular signal: environmental regulation of Salmonella virulence. Cell 84: 165– 174.

45. Garner, R. M.,, J. F. Fulkerson,, and H. L. Mobley. 1998. Helicobacter pylori glutamine synthetase lacks features associated with transcriptional and posttranslational regulation. Infect. Immun. 66: 1839– 1847.

46. Ge, Z.,, K. Hiratsuka,, and D. E. Taylor. 1995. Nucleotide sequence and mutational analysis indicate that two Helicobacter pylori genes encode a P-type ATPase and a cation-binding protein associated with copper transport. Mol. Microbiol. 15: 97– 106.

47. Ge, Z.,, and D. E. Taylor. 1996. Helicobacter pylori genes hpcopA and hpcopP constitute a cop operon involved in copper export. FEMS Microbiol. Lett. 145: 181– 188.

48. Ge, Z.,, and D. E. Taylor. 1996. Sequencing, expression, and genetic characterization of the Helicobacter pylori ftsH gene encoding a protein homologous to members of a novel putative ATPase family. J. Bacteriol. 178: 6151– 6157.

49. Gilbert, J. V.,, J. Ramakrishna,, F. W. Sunderman, Jr.,, A. Wright,, and A. G. Plaut. 1995. Protein Hpn: cloning and characterization of a histidine-rich metal-binding polypeptide in Helicobacter pylori and Helicobacter mustelae. Infect. Immun. 63: 2682– 2688.

50. Grunden, A. M.,, and K. T. Shanmugam. 1997. Molybdate transport and regulation in bacteria. Arch. Microbiol. 168: 345– 354.

51. Hantke, K. 1997. Ferrous iron uptake by a magnesium transport system is toxic for Escherichia coli and Salmonella typhimurium. J. Bacteriol. 179: 6201– 6204.

52. Harold, F. M.,, and P. C. Maloney,. 1996. Energy transduction by ion currents, p. 283– 306. In F. C. Neidhardt (ed.), Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd ed. ASM Press, Washington, D.C.

53. Harrison, M. D.,, C. E. Jones,, M. Solioz,, and C. T. Dameron. 2000. Intracellular copper routing: the role of copper chaperones. Trends Biochem. Sci. 25: 29– 32.

54. Hawtin, P. R.,, H. T. Delves,, and D. G. Newell. 1991. The demonstration of nickel in the urease of Helicobacter pylori by atomic absorption spectroscopy. FEMS Microbiol. Lett. 61: 51– 54.

55. Hendricks, J. K.,, and H. L. Mobley. 1997. Helicobacter pylori ABC transporter: effect of allelic exchange mutagenesis on urease activity. J. Bacteriol. 179: 5892– 5902.

56. Herrmann, L.,, D. Schwan,, R. Garner,, H. L. Mobley,, R. Haas,, K. P. Schafer,, and K. Melchers. 1999. Helicobacter pylori cadA encodes an essential Cd(II)-Zn(II)-Co(II) resistance factor influencing urease activity. Mol. Microbiol. 33: 524– 536.

57. Hu, L. T.,, P. A. Foxall,, R. Russell,, and H. L. Mobley. 1992. Purification of recombinant Helicobacter pylori urease apoenzyme encoded by ureA and ureB. Infect. Immun. 60: 2657– 2666.

58. Husson, M. O.,, D. Legrand,, G. Spik,, and H. Leclerc. 1993. Iron acquisition by Helicobacter pylori: importance of human lactoferrin. Infect. Immun. 61: 2694– 2697.

59. Illingworth, D. S.,, K. S. Walter,, P. L. Griffiths,, and R. Barclay. 1993. Siderophore production and iron-regulated envelope proteins of Helicobacter pylori. Int. J. Med. Microbiol. Virol. Parasitol. Infect. Dis. 280: 113– 119.

60. Inoue, H.,, T. Sakurai,, S. Ujike,, T. Tsuchiya,, H. Murakami,, and H. Kanazawa. 1999. Expression of functional Na +/H + antiporters of Helicobacter pylori in antiporter-deficient Echerichia coli mutants. FEBS Lett. 443: 11– 16.

61. Kaihovaara, P.,, K. S. Salmela,, R. P. Roine,, T. U. Kosunen,, and M. Salaspuro. 1994. Purification and characterization of Helicobacter pylori alcohol dehydrogenase. Alcohol Clin. Exp. Res. 18: 1220– 1225.

62. Kammler, M.,, C. Schon,, and K. Hantke. 1993. Characterization of the ferrous iron uptake system of Escherichia coli. J. Bacteriol. 175: 6212– 6219.

63. Kansau, I.,, F. Guillain,, J. M. Thiberge,, and A. Labigne. 1996. Nickel binding and immunological properties of the C-terminal domain of the Helicobacter pylori GroES homologue (HspA). Mol. Microbiol. 22: 1013– 1023.

64. Krishnamurthy, P.,, M. Parlow,, J. B. Zitzer,, N. B. Vakil,, H. L. Mobley,, M. Levy,, S. H. Phadnis,, and B. E. Dunn. 1998. Helicobacter pylori containing only cytoplasmic urease is susceptible to acid. Infect. Immun. 66: 5060– 5066.

65. Larsen, R. A.,, D. Foster-Hartnett,, M. A. Mcintosh,, and K. Postle. 1997. Regions of Escherichia coli TonB and FepA proteins essential for in vivo physical interactions. J. Bacteriol. 179: 3213– 3221.

66. Litwin, C. M.,, and S. B. Calderwood. 1993. Role of iron in regulation of virulence genes. Clin. Microbiol. Rev. 6: 137– 149.

67. Maier, R. J.,, C. Fu,, J. Gilbert,, F. Mosbiri,, J. Olson,, and A. G. Plaut. 1996. Hydrogen uptake hydrogenase in Helicobacter pylori. FEMS Microbiol. Lett. 141: 71– 76.

68. Manos, J.,, T. Kolesnikow,, and S. L. Hazell. 1998. An investigation of the molecular basis of the spontaneous occurrence of a catalase-negative phenotype in Helicobacter pylori. Helicobacter 3: 28– 38.

69. Marshall, B. J.,, and J. R. Warren. 1984. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet i: 1311– 1315.

70. Melchers, K.,, L. Herrmann,, F. Mauch,, D. Bayle,, D. Heuermann,, T. Weitzenegger,, A. Schuhmacher,, G. Sachs,, R. Haas,, G. Bode,, K. Bensch,, and K. P. Schafer. 1998. Properties and function of the P type ion pumps cloned from Helicobacter pylori. Acta Physiol. Scand. Suppl. 643: 123– 135.

71. Melchers, K.,, A. Schuhmacher,, A. Buhmann,, T. Weitzenegger,, D. Belin,, S. Grau,, and M. Ehrmann. 1999. Membrane topology of CadA homologous P-type ATPase of Helicobacter pylori as determined by expression of phoA fusions in Escherichia coli and the positive inside rule. Res. Microbiol. 150: 507– 520.

72. Melchers, K.,, T. Weitzenegger,, A. Buhmann,, W. Steinhilber,, G. Sachs,, and K. P. Schafer. 1996. Cloning and membrane topology of a P type ATPase from Helicobacter pylori. J. Biol. Chem. 271: 446– 457.

73. Melchers, K.,, T. Wiegert,, A. Buhmann,, S. Postius,, K. P. Schafer,, and W. Schumann. 1998. The Helicobacter felis ftsH gene encoding an ATP-dependent metalloprotease can replace the Escherichia coli homologue for growth and phage lambda lysogenization. Arch. Microbiol. 169: 393– 396.

74. Miller, R. A.,, and B. E. Britigan. 1999. Role of oxidants in microbial pathophysiology. Clin. Microbiol. Rev. 10: 1– 18.

75. Mobley, H. L. 1996. The role of Helicobacter pylori urease in the pathogenesis of gastritis and peptic ulceration. Aliment. Pharmacol. Ther. 10: 57– 64.

76. Mobley, H. L.,, R. M. Garner,, and P. Bauerfeind. 1995. Helicobacter pylori nickel-transport gene nixA: synthesis of catalytically active urease in Escherichia coli independent of growth conditions. Mol. Microbiol. 16: 97– 109.

77. Mobley, H. L.,, R. M. Garner,, G. R. Chippendale,, J. V. Gilbert,, A. V. Kane,, and A. G. Plaut. 1999. Role of Hpn and NixA of Helicobacter pylori in susceptibility and resistance to bismuth and other metal ions. Helicobacter 4: 162– 169.

78. Mobley, H. L.,, M. D. Island,, and R. P. Hausinger. 1995. Molecular biology of microbial ureases. Microbiol. Rev. 59: 451– 480.

79. Moeck, G. S.,, and J. W. Coulton. 1998. TonB-dependent iron acquisition: mechanisms of siderophore-mediated active transport. Mol. Microbiol. 28: 675– 681.

80. Mori, M.,, H. Suzuki,, M. Suzuki,, A. Kai,, S. Miura,, and H. Ishii. 1997. Catalase and superoxide dismutase secreted from Helicobacter pylori. Helicobacter 2: 100– 105.

81. Nagata, K.,, S. Tsukita,, T. Tamura,, and N. Sone. 1996. A cb-type cytochrome-c oxidase terminates the respiratory chain in Helicobacter pylori. Microbiology 142: 1757– 1763.

82. Namavar, F.,, M. Sparrius,, E. C. Veerman,, B. J. Appelmelk,, and C. M. J. E. Vandenbroucke-Grauls. 1998. Neutrophil-activating protein mediates adhesion of Helicobacter pylori to sulfated carbohydrates on high-molecular-weight salivary mucin. Infect. Immun. 66: 444– 447.

83. Navarro, C.,, L. F. Wu,, and M. A. Mandrand-Berthelot. 1993. The nik operon of Escherichia coli encodes a periplasmic binding-protein-dependent transport system for nickel. Mol. Microbiol. 9: 1181– 1191.

84. Neilands, J. B. 1995. Siderophores: structure and function of microbial iron transport compounds. J. Biol. Chem. 270: 26723– 26726.

85. Nikaido, H., 1996. Outer membrane, p. 29– 47. In F. C. Neidhardt (ed.), Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd ed. ASM Press, Washington, D.C.

86. Occhino, D. A.,, E. E. Wyckoff,, D. P. Henderson,, T. J. Wrona,, and S. M. Payne. 1998. Vibrio cholerae iron transport: haem transport genes are linked to one of two sets of tonB, exbB, exbD genes. Mol. Microbiol. 29: 1493– 1507.

87. Odenbreit, S.,, B. Wieland,, and R. Haas. 1996. Cloning and genetic characterization of Helicobacter pylori catalase and construction of a catalase-deficient mutant strain. J. Bacteriol. 178: 6960– 6967.

88. O'Toole, P. W.,, S. M. Logan,, M. Kostrzynska,, T. Wadstrom,, and T.J. Trust. 1991. Isolation and biochemical and molecular analyses of a species-specific protein antigen from the gastric pathogen Helicobacter pylori. J. Bacteriol. 173: 505– 513.

89. Perez-Perez, G. I.,, C. B. Gower,, and M. J. Blaser. 1994. Effects of cations on Helicobacter pylori urease activity, release, and stability. Infect. Immun. 62: 299– 302.

90. Pesci, E. C.,, and C. L. Pickett. 1994. Genetic organization and enzymatic activity of a superoxide dismutase from the microaerophilic human pathogen, Helicobacter pylori. Gene 143: 111– 116.

91. Pressler, U.,, H. Staudenmaier,, L. Zimmermann,, and V. Braun. 1988. Genetics of the iron dicitrate transport system of Escherichia coli. J. Bacteriol. 170: 2716– 2724.

92. Rajagopalan, K. V., 1996. Biosynthesis of the molybdenum cofactor, p. 674– 679. In F. C. Neidhardt (ed.), Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd ed. ASM Press, Washington, D.C.

93. Reuter, K.,, and R. Ficner. 1995. Sequence analysis and over-expression of the Zymomonas mobilis tgt gene encoding tRNA-guanine transglycosylase: purification and biochemical characterization of the enzyme. J. Bacteriol. 177: 5284– 5288.

94. Reuter, K.,, R. Slany,, F. Ullrich,, and H. Kersten. 1991. Structure and organization of Escherichia coli genes involved in biosynthesis of the deazaguanine derivative queuine, a nutrient factor for eukaryotes. J. Bacteriol. 173: 2256– 2264.

95. Richardson, P. T.,, and S. F. Park. 1995. Enterochelin acquisition in Campylobacter coli—characterization of components of a binding protein dependent transport system. Microbiology 141: 3181– 3191.

96. Salmela, K. S.,, R. P. Roine,, T. Koivisto,, J. Hook-Nikanne,, T. U. Kosunen,, and M. Salaspuro. 1993. Characteristics of Helicobacter pylori alcohol dehydrogenase. Gastroenterology 105: 325– 330.

97. Scarlato, V.,, and R. Rappuoli. 1991. Differential response of the bvg virulence regulon of Bordetella pertussis to MgSO 4 modulation. J. Bacteriol. 173: 7401– 7404.

98. Schumann, W. 1999. FtsH—a single chain charonin? FEMS Microbiol. Rev. 23: 1– 11.

99. Scott, D. R.,, D. Weeks,, C. Hong,, S. Postius,, K. Melchers,, and G. Sachs. 1998. The role of internal urease in acid resistance of Helicobacter pylori. Gastroenterology 114: 58– 70.

100. Silver, S., 1996. Transport of inorganic cations, p. 1091– 1102. In F. C. Neidhardt (ed.), Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd ed. ASM Press, Washington, D.C.

101. Silver, S.,, and L. T. Phung. 1996. Bacterial heavy metal resistance: new surprises. Annu. Rev. Microbiol. 50: 753– 789.

102. Smith, R. L.,, and M. E. Maguire. 1998. Microbial magnesium transport: unusual transporters searching for identity. Mol. Microbiol. 28: 217– 226.

103. Spiegelhalder, C.,, B. Gerstenecker,, A. Kersten,, E. Schiltz,, and M. Kist. 1993. Purification of Helicobacter pylori superoxide dismutase and cloning and sequencing of the gene. Infect. Immun. 61: 5315– 5325.

104. Spohn, G.,, and V. Scarlato. 1999. The autoregulatory HspR repressor protein governs chaperone gene transcription in Helicobacter pylori. Mol. Microbiol. 34: 663– 674.

105. Stojiljkovic, I.,, M. Cobeljic,, and K. Hantke. 1993. Escherichia coli K-12 ferrous iron uptake mutants are impaired in their ability to colonize the mouse intestine. FEMS Microbiol. Lett. 108: 111– 115.

106. Sunderman, F. W. 1993. Biological monitoring of nickel in humans. Scand. J. Work. Environ. Health 19( Suppl. 1): 34– 38.

107. Szczebara, F.,, L. Dhaenens,, S. Armand,, and M. O. Husson. 1999. Regulation of the transcription of genes encoding different virulence factors in Helicobacter pylori by free iron. FEMS Microbiol. Lett. 175: 165– 170.

108. Tomb, J. F.,, O. White,, A. R. Kerlavage,, R. A. Clayton,, G. G. Sutton,, R. D. Fleischmann,, K. A. Ketchum,, H. P. Klenk,, S. Gill,, B. A. Dougherty,, K. Nelson,, J. Quackenbush,, L. Zhou,, E. F. Kirkness,, S. Peterson,, B. Loftus,, D. Richardson,, R. Dodson,, H. G. Khalak,, A. Glodek,, K. McKenney,, L. M. Fitzegerald,, N. Lee,, M. D. Adams,, E. K. Hickey,, D. E. Berg,, J. D. Gocayne,, T. R. Utterback,, J. D. Peterson,, J. M. Kelley,, M. D. Cotton,, J. M. Weidman,, C. Fujii,, C. Bowman,, L. Watthey,, E. Wallin,, W. S. Hayes,, M. Borodovsky,, P. D. Karp,, H. O. Smith,, C. M. Fraser,, and J. C. Venter. 1997. The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature 388: 539– 547.

109. Tonello, F.,, W. G. Dundon,, B. Satin,, M. Molinari,, G. Tognou,, G. Grandi,, G. del Guicide,, R. Rappuoli,, and C. Montecucco. 1999. The Helicobacter pylori neutrophil-activating protein is an iron-binding protein with dodecameric structure. Mol. Microbiol. 34: 238– 246.

110. Touati, D. 2000. Iron and oxidative stress in bacteria. Arch. Biochem. Biophys. 373: 1– 6.

111. Tsolis, R. M.,, A. J. Baumler,, F. Heffron,, and I. Stojiljkovic. 1996. Contribution of tonB- and feo-mediated iron uptake to growth of Salmonella typhimurium in the mouse. Infect. Immun. 64: 4549– 4556.

112. Tsukita, S.,, S. Koyanagi,, K. Nagata,, H. Koizuka,, H. Akashi,, T. Shimoyama,, T. Tamura,, and N. Sone. 1999. Characterization of a cb-type cytochrome c oxidase from Helicobacter pylori. J. Biochem. 125: 194– 201.

113. van Vliet, A. H. M.,, S. Bereswill,, B. Waidner,, E. J. Kuipers,, C. M. J. E. Vandenbroucke-Grauls,, and J. G. Kusters. 2000. Fur-mediated nickel-responsive regulation of urease expression in Helicobacter pylori. Gut 47( S1): A17– A18.

114. van Vliet, A. H. M.,, N. de Vries,, S. Bereswill,, M. Kist,, E. J. Kuipers,, C. M. J. E. Vandenbroucke-Grauls,, and J. G. Kusters. 1999. The role of the ferric uptake regulator (Fur) protein in Helicobacter pylori iron uptake. Gut 45( S3): A27.

115. Velayudhan, J.,, N. J. Hughes,, A. A. McColm,, J. Bagshaw,, C. L. Clayton,, S. C. Andrews,, and D. J. Kelly. 2000. Iron acquisition and virulence in Helicobacter pylori: a major role for FeoB, a high-affinity ferrous iron transporter. Mol. Microbiol. 37: 274– 286.

116. Waidner, B.,, S. Greiner,, M. Kist,, and S. Bereswill. 2000. Regulation and functions of prokaryotic ferritin in Helicobacter pylori. Gut 47( S1): A3.

117. Warren, J. R.,, and B. J. Marshall. 1983. Unidentified curved bacilli on gastric epithelium in chronic active gastritis. Lancet i: 1273– 1275.

118. Weeks, D. I.,, S. Eskandari,, D. R. Scott,, and G. Sachs. 2000. A H +-gated urea channel: the link between Helicobacter pylori urease and gastric colonization. Science 287: 482– 485.

119. Westblom, T. U.,, S. Phadnis,, W. Langenberg,, K. Yoneda,, E. Madan,, and B. R. Midkiff. 1992. Catalase negative mutants of Helicobacter pylori. Eur. J. Clin. Microbiol. Infect. Dis. 11: 522– 526.

120. Windle, H. J.,, and D. Kelleher. 1997. Identification and characterization of a metalloprotease activity from Helicobacter pylori. Infect. Immun. 65: 3132– 3137.

121. Worst, D. J.,, M. M. Gerrits,, C. M. J. E. Vandenbroucke-Grauls,, and J. G. Kusters. 1998. Helicobacter pylori ribBA-mediated riboflavin production is involved in iron acquisition. J. Bacteriol. 180: 1473– 1479.

122. Worst, D.J.,, B.R. Otto,andJ.deGraaff. 1995. Iron-repressible outer membrane proteins of Helicobacter pylori involved in heme uptake. Infect. Immun. 63: 4161– 4165.

123. Worst, D. J.,, M. Sparrius,, E. J. Kuipers,, J. G. Kusters,, and J. de Graaff. 1996. Human serum antibody response against iron-repressible outer membrane proteins of Helicobacter pylori. FEMS Microbiol. Lett. 144: 29– 32.