1887

Abstract

Short nucleotide sequence inserts within the signal (s) and mid (m) regions of the vacuolating cytotoxin gene () of provide the basis for defining the allelic forms widely used for strain typing and as markers for toxin functionality and severity of interactions with host gastric epithelial cells. Here 484 signal region and 411 mid-region sequences (new and from public databases) from 32 countries were analysed to determine the effect of geographical location on insert diversity, which is currently undefined. Short (27 bp) inserts of 52 mol% G+C from 201 sequences (98 %) of the s2 allelic family encoded a highly conserved nine amino acid sequence irrespective of geographical origin. The longer (75 bp) mid-region insert of 38 mol% G+C in 255 sequences of the m2 allelic family was more diverse and represented by 23 peptide variants, with one predominant sequence (MRI type 4) representing 62 % of inserts. Mid-region inserts were widespread throughout European/North American (Western) sequences in the dataset whereas a lower insert frequency was a geographical feature of East Asian sequences. Each insert was preceded by an associated conserved motif that provided a marker of the insertion sites within A, and facilitated identification of the Chinese m2b genotype. It is concluded that the observed sequence conservation supports the continued global use of genotyping, and that inserts could have a functional significance in the mature protein, particularly the s2 form of the toxin, as the same combination of signal and mid-region insert type and preinsert motif was highly conserved.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.2006/002923-0
2007-04-01
2019-10-20
Loading full text...

Full text loading...

/deliver/fulltext/micro/153/4/1176.html?itemId=/content/journal/micro/10.1099/mic.0.2006/002923-0&mimeType=html&fmt=ahah

References

  1. Aceti, A., Are, R., Sabino, G., Fenu, L., Pasquazzi, C., Quaranta, G., Zechini, B. & Terrosu, P. ( 2004; ). Helicobacter pylori active infection in patients with acute coronary heart disease. J Infect 49, 8–12.[CrossRef]
    [Google Scholar]
  2. Achtman, M., Azuma, T., Berg, D. E., Ito, Y., Morelli, G., Pan, Z. J., Suerbaum, S., Thompson, S. A., van der Ende, A. & van Doorn, L. J. ( 1999; ). Recombination and clonal groupings within Helicobacter pylori from different geographical regions. Mol Microbiol 32, 459–470.[CrossRef]
    [Google Scholar]
  3. Alm, R. A., Ling, L. S., Moir, D. T., King, B. L., Brown, E. D., Doig, P. C., Smith, D. R., Noonan, B., Guild, B. C. & other authors ( 1999; ). Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature 397, 176–180.[CrossRef]
    [Google Scholar]
  4. Andreson, H., Lōivukene, K., Sillakivi, T., Maaroos, H. I., Ustav, M., Peetsla, A. & Mikelsaar, M. ( 2002; ). Association of cagA and vacA genotypes of Helicobacter pylori with gastric diseases in Estonia. J Clin Microbiol 40, 298–300.[CrossRef]
    [Google Scholar]
  5. Apostolov, E., Al-Soud, W. A., Nilsson, I., Kornilovska, I., Usenko, V., Lyzoqubov, V., Gaydar Y., Wadstron, T. & Ljungh, A. ( 2005; ). Helicobacter pylori and other Helicobacter species in gall bladder and liver of patients with chronic cholecystitis detected by immunological and molecular methods. Scand J Gastroenterol 40, 96–102.[CrossRef]
    [Google Scholar]
  6. Atherton, J. C., Cao, P., Peek, R. M., Jr, Tummuru, M. K., Bllaser, M. J. & Cover, T. L. ( 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.[CrossRef]
    [Google Scholar]
  7. Atherton, J. C., Sharp, P. M. & Cover, T. L. ( 1999a; ). Vacuolating cytotoxin (vacA) alleles of Helicobacter pylori comprise two geographically widespread types, m1 and m2, and have evolved through limited recombination. Curr Microbiol 39, 211–218.[CrossRef]
    [Google Scholar]
  8. Atherton, J. C., Cover, T. L., Twells, R. J., Hawkey, C. J. & Blaser, M. J. ( 1999b; ). Simple and accurate PCR-based system for typing vacuolating cytotoxin alleles of Helicobacter pylori. J Clin Microbiol 37, 2979–2982.
    [Google Scholar]
  9. Azuma, T., Kato, S., Zhou, W., Yamazaki, S., Yamakawa, A., Ohtani, M., Fujiwara, S., Minoura, T., Iinuma, K. & Kato, T. ( 2004; ). Diversity of vacA and cagA genes of Helicobacter pylori in Japanese children. Aliment Pharmacol Ther 20, 7–12.
    [Google Scholar]
  10. Blaser, M. J. ( 1999; ). Allelic variation in Helicobacter pylori: progress but no panacea. Gut 45, 499–502.[CrossRef]
    [Google Scholar]
  11. Blaser, M. J. & Atherton, J. C. ( 2004; ). Helicobacter pylori persistence: biology and disease. J Clin Invest 113, 321–333.[CrossRef]
    [Google Scholar]
  12. Boquet, P., Ricci, V., Galmiche, A. & Gauthier, N. C. ( 2003; ). Gastric cell apoptosis and Helicobacter pylori: has the main function of vacA finally been identified? Trends Microbiol 11, 410–413.[CrossRef]
    [Google Scholar]
  13. Campbell, S., Fraser, A., Holliss, B., Schmid, J. & O'Toole, P. W. ( 1997; ). Evidence for ethnic tropism of Helicobacter pylori. Infect Immun 65, 3708–3712.
    [Google Scholar]
  14. Cao, P., Lee, K. J., Blaser, M. J. & Cover, T. L. ( 2005; ). Analysis of hopQ alleles in East Asian and Western strains of Helicobacter pylori. FEMS Microbiol Lett 251, 37–43.[CrossRef]
    [Google Scholar]
  15. Cooper, J. E. & Feil, E. J. ( 2004; ). Multilocus sequence typing – what is resolved? Trends Microbiol 12, 373–377.[CrossRef]
    [Google Scholar]
  16. Covacci, A., Telford, J. L., Del Guidice, G., Parsonnet, J. & Rappuoli, R. ( 1999; ). Helicobacter pylori virulence and genetic geography. Science 284, 1328–1333.[CrossRef]
    [Google Scholar]
  17. Cover, T. L. & Blanke, S. R. ( 2005; ). Helicobacter pylori vacA, a paradigm for toxin multifunctionality. Nat Rev Microbiol 3, 320–332.[CrossRef]
    [Google Scholar]
  18. Elviss, N. C., Owen, R. J., Xerry, J., Walker, A. M. & Davies, K. ( 2004; ). Helicobacter pylori antibiotic resistance patterns and genotypes in adult dyspeptic patients from a regional population in North Wales. J Antimicrob Chemother 54, 435–440.[CrossRef]
    [Google Scholar]
  19. Elviss, N. C., Owen, R. J., Breathnach, A., Palmer, C. & Shetty, N. ( 2005; ). Helicobacter pylori antibiotic-resistance patterns and risk factors in adult dyspeptic patients from ethnically diverse population in Central and South London during 2000. J Med Microbiol 54, 567–574.[CrossRef]
    [Google Scholar]
  20. Falush, D., Kraft, C., Taylor, N. S., Correa, P., Fox, J. G., Achtman, M. & Suerbaum, S. ( 2001; ). Recombination and mutation during long-term gastric colonization by Helicobacter pylori: estimates of clock rates, recombination size, and minimal age. Proc Natl Acad Sci U S A 98, 15056–15061.[CrossRef]
    [Google Scholar]
  21. Falush, D., Wirth, T., Linz, B., Pritchard, J. K., Stephens, M., Kidd, M., Blaser, M. J., Graham, D. Y., Vacher, S. & other authors ( 2003; ). Traces of human migrations in Helicobacter pylori populations. Science 299, 1582–1585.[CrossRef]
    [Google Scholar]
  22. Gebert, B., Fischer, W. & Haas, R. ( 2004; ). The Helicobacter pylori vacuolating cytotoxin: from cellular vacuolation to immunosuppressive activities. Rev Physiol Biochem Pharmacol 152, 205–220.
    [Google Scholar]
  23. Ghose, C., Perez-Perez, G. I., Dominguez-Bello, M. G., Pride, D. T., Bravi, C. M. & Blaser, M. J. ( 2002; ). East Asian genotypes of Helicobacter pylori strains in Amerindians provide evidence for its ancient human carriage. Proc Natl Acad Sci U S A 99, 15107–15111.[CrossRef]
    [Google Scholar]
  24. Go, M. F., Cissell, L. & Graham, D. Y. ( 1998; ). Failure to confirm association of vacA gene mosaicism with duodenal ulcer disease. Scand J Gastroenterol 33, 132–136.[CrossRef]
    [Google Scholar]
  25. Gong, Y. H., Wang, Y. & Yuan, Y. ( 2005; ). Distribution of Helicobacter pylori in North China. World J Gastroenterol 11, 3523–3527.[CrossRef]
    [Google Scholar]
  26. Gressmann, H., Linz, B., Ghai, R., Pleissner, K. P., Schlapbach, R., Yamaoka, Y., Kraft, C., Suerbaum, S., Meyer, T. F. & Achtman, M. ( 2005; ). Gain and loss of multiple genes during the evolution of Helicobacter pylori. PloS Genetics 1, 419–427.
    [Google Scholar]
  27. Hall, T. A. ( 1999; ). BioEdit: a user friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser 41, 95–98.
    [Google Scholar]
  28. Höcker, M. & Hohenberger, P. ( 2003; ). Helicobacter pylori virulence factors – one part of a big picture. Lancet 362, 1231–1233.[CrossRef]
    [Google Scholar]
  29. Huang, Y., Fan, X. G., Wang, Z. M., Zhou, J. H., Tian, X. F. & Li, N. ( 2004; ). Identification of Helicobacter species in human liver samples from patients with primary hepatocellular carcinoma. J Clin Pathol 57, 1273–1277.[CrossRef]
    [Google Scholar]
  30. Ito, Y., Azuma, T., Ito, S., Miyaji H., Hirai, M., Yamazaki, Y., Sato, F., Kato, T., Kohli, Y. & Kuriyama, M. ( 1997; ). Analysis and typing of the vacA gene from cagA-positive strains of Helicobacter pylori isolated in Japan. J Clin Microbiol 35, 1710–1714.
    [Google Scholar]
  31. Ji, X., Fernandez, T., Burroni, D., Pagliaccia, C., Atherton, J. C., Reyrat, J. M., Rappuoli, R. & Telford, J. L. ( 2000; ). Cell specificity of Helicobacter pylori cytotoxin is determined by a short region in the polymorphic midregion. Infect Immun 68, 3754–3757.[CrossRef]
    [Google Scholar]
  32. Ji, X., Frati, F., Barone, S., Pagliaccia, C., Burroni, D., Xu, G., Rappuoli, R., Reyrat, J. M. & Telford, J. L. ( 2002; ). Evolution of functional polymorphism in the gene coding for the Helicobacter pylori cytotoxin. FEMS Microbiol Lett 206, 253–258.[CrossRef]
    [Google Scholar]
  33. Jukes, T. H. & Cantor, C. R. ( 1969; ). Evolution of protein molecules. In Mammalian Protein Metabolism III, pp. 21–32. edited by H. N. Munro. New York: Academic Press.
  34. Kauser, F., Hussain, M. A., Ahmed, I., Srinivas, S., Devi, S. M., Majeed, A. A., Rao, K. R., Khan, A. A., Sechi, L. A. & Ahmed, N. ( 2005; ). Comparative genomics of Helicobacter pylori isolates recovered from ulcer disease patients in England. BMC Microbiol 5, 32.[CrossRef]
    [Google Scholar]
  35. Kersulyte, D., Mukhopadhyay, A. K., Velapatiño, B., Su, W., Pan, Z., Garcia, C., Hernandez, V., Valdez, Y., Mistry, R. S. & other authors ( 2000; ). Differences in genotypes of Helicobacter pylori from different human populations. J Bacteriol 182, 3210–3218.[CrossRef]
    [Google Scholar]
  36. Lambert, R., Guilloux, A., Oshima, A., Pompe-Kirn, V., Bray, F., Parkin, M., Ajiki, W. & Tsukuma, H. ( 2002; ). Incidence and mortality from stomach cancer in Japan, Slovenia and the USA. Int J Cancer 97, 811–818.[CrossRef]
    [Google Scholar]
  37. Lee, A., O'Rourke, J., De Ungria, M. C., Robertson, B., Daskalopoulos, G. & Dixon, M. F. ( 1997; ). A standardized mouse model of Helicobacter pylori infection: introducing the Sydney strain. Gastroenterology 112, 1386–1397.[CrossRef]
    [Google Scholar]
  38. Letley, D. P. & Atherton, J. C. ( 2000; ). Natural diversity in the N terminus of the mature vacuolating cytotoxin of Helicobacter pylori determines cytotoxin activity. J Bacteriol 182, 3278–3280.[CrossRef]
    [Google Scholar]
  39. Letley, D. P., Lastovica, A., Louw, J. A., Hawkey, C. J. & Atherton, J. C. ( 1999; ). Allelic diversity of the Helicobacter pylori vacuolating cytotoxin gene in South Africa: rarity of the vacA s1a genotype and natural occurrence of an s2/m1 allele. J Clin Microbiol 37, 1203–1205.
    [Google Scholar]
  40. Letley, D. P., Rhead, J. L., Twells, R. J., Dove, B. & Atherton, J. C. ( 2003; ). Determinants of non-toxicity in the gastric pathogen Helicobacter pylori. J. Biol Chem 278, 26734–26741.[CrossRef]
    [Google Scholar]
  41. McClain, M. S., Cao, P., Iwamoto, H., Vinion-Dubiel, A. D., Szabo, G., Shao, Z. & Cover, T. L. ( 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.[CrossRef]
    [Google Scholar]
  42. Naylor, G. M., Gotoda, T., Dixon, M., Shimoda, T., Gatta, L., Owen, R., Tompkins, D. & Axon, A. ( 2006; ). Why does Japan have a high incidence of gastric cancer? Comparison of gastritis between UK and Japanese patients. Gut 55, 1545–1552.[CrossRef]
    [Google Scholar]
  43. Neugut, A. I., Hayek, H. & Howe, G. ( 1996; ). Epidemiology of gastric cancer. Semin Oncol 23, 281–291.
    [Google Scholar]
  44. Owen, R. J., Xerry, J., Peters, T. M. & Teare, E. L. ( 2002; ). Surveillance and clinical relevance of vacA genotypes of Helicobacter pylori infecting dyspeptic patients in mid Essex. Commun Dis Public Health 5, 106–111.
    [Google Scholar]
  45. Owen, R. J., Xerry, J., Gotada, T., Naylor, G. & Tompkins, D. ( 2004; ). Analysis of geospecific markers for Helicobacter pylori variants in patients from Japan and Nigeria by triple-locus nucleotide sequence typing. Microbiology 150, 151–161.[CrossRef]
    [Google Scholar]
  46. Pagliaccia, C., de Bernard, M., Lupetti, P., Ji, X., Burroni, D., Cover, T. L., Papinin, E., Rappuoli, R., Telford, J. L. & Reyrat, J. M. ( 1998; ). The m2 form of the Helicobacter pylori cytotoxin has cell type-specific vacuolating activity. Proc Natl Acad Sci U S A 95, 10212–10217.[CrossRef]
    [Google Scholar]
  47. Pan, Z. J., Berg, D. E., van der Hulst, R. W., Su, W. W., Raudoikiene, A., Xiao, S. D., Dankert, J., Tygat, G. N. & van der Ende, A. ( 1998; ). Prevalence of vacuolating cytotoxin production and distribution of distinct vacA alleles in Helicobacter pylori from China. J Infect Dis 178, 220–226.[CrossRef]
    [Google Scholar]
  48. Pounder, R. E. & Ng, D. ( 1995; ). The prevalence of Helicobacter pylori infection in different countries. Aliment Pharmacol Ther 9, 33–39.
    [Google Scholar]
  49. Qiao, W., Hu, J. L., Xiao, B., Wu, K. C., Peng, D. R., Atherton, J. C. & Xue, H. ( 2003; ). cagA and vacA genotype of Helicobacter pylori associated with gastric diseases in Xi'an area. World J Gastroenterol 9, 1762–1766.
    [Google Scholar]
  50. Saitou, N. & Nei, M. ( 1987; ). The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4, 406–425.
    [Google Scholar]
  51. Suerbaum, S. & Achtman, M. ( 2004; ). Helicobacter pylori: recombination, population structure and human migrations. Int J Med Microbiol 294, 133–139.[CrossRef]
    [Google Scholar]
  52. Suerbaum, S. & Michetti, P. ( 2002; ). Helicobacter pylori infection. N Engl J Med 347, 1175–1186.[CrossRef]
    [Google Scholar]
  53. Suerbaum, S., Smith, J. M., Bapumia, K., Morelli, G., Smith, N. H., Kunstmann, E., Dyrek, I. & Achtman, M. ( 1998; ). Free recombination within Helicobacter pylori. Proc Natl Acad Sci U S A 95, 12619–12624.[CrossRef]
    [Google Scholar]
  54. Suerbaum, S., Josenhans, C., Sterzenbach, T., Drescher, B., Brandt, P., Bell, M., Droge, M., Fartmann, B., Fischer, H. P. & other authors ( 2003; ). The complete genome sequence of the carcinogenic bacterium Helicobacter hepaticus. Proc Natl Acad Sci U S A 100, 7901–7906.[CrossRef]
    [Google Scholar]
  55. Tomb, J. F., White, O., Kerlavage, A. R., Clayton, R. A., Sutton, G. G., Fleischmann, R. D., Ketchum, K. A., Klenk, H. P., Gill, S. & other authors ( 1997; ). The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature 388, 539–547.[CrossRef]
    [Google Scholar]
  56. van de Peer, Y. & de Wachter, R. ( 1994; ). treecon for Windows: a software package for the construction and drawing of evolutionary trees for the Microsoft Windows environment. Comput Appl Biosci 10, 569–570.
    [Google Scholar]
  57. van der Ende, A., Pan, Z. J., Bart, A., van der Hulst, R. W., Feller, M., Xiao, S. D., Tygat, G. N. & Dankert, J. ( 1998; ). cagA-positive Helicobacter pylori populations in China and The Netherlands are distinct. Infect Immun 66, 1822–1826.
    [Google Scholar]
  58. van Doorn, L. J., Figueiredo, C., Sanna, R., Pena, S., Midolo, P., Ng, E. K., Atherton, J. C., Blaser, M. J. & Quint, W. G. ( 1998; ). Expanding allelic diversity of Helicobacter pylori vacA. J Clin Microbiol 36, 2597–2603.
    [Google Scholar]
  59. van Doorn, L. J., Figueiredo, C., Megraud, F., Pena, S., Midolo, P., Queiroz, D. M., Carneiro, F., Vanderborght, B., Pegado, M. D. & other authors ( 1999; ). Geographic distribution of vacA allelic types of Helicobacter pylori. Gastroenterology 116, 823–830.[CrossRef]
    [Google Scholar]
  60. Wang, J., van Doorn, L.-J., Robinson, P. A., Ji, X., Wang, D., Wang, Y., Ge, L., Telford, J. L. & Crabtree, J. E. ( 2003; ). Regional variation among vacA alleles of Helicobacter pylori in China. J Clin Microbiol 41, 1942–1945.[CrossRef]
    [Google Scholar]
  61. Wilson, K. ( 1987; ). Preparation of genomic DNA from bacteria. In Current Protocols in Molecular Biology, pp. 241–245. Edited by F. M. Ausubel, R. Brent, R. E. Kingston, D. D. Moore, J. A. Smith, J. G. Seidman & K. Struh. New York: Wiley.
  62. Wirth, T., Wang, X., Linz, B., Novick, R. P., Lum, J. K., Blaser, M., Morelli, G., Falush, D. & Achtman, M. ( 2004; ). Distinguishing human ethnic groups by means of sequences from Helicobacter pylori: lessons from Ladakh. Proc Natl Acad Sci U S A 101, 4746–4751.[CrossRef]
    [Google Scholar]
  63. Yakoob, J., Fan, X. G., Peng, X. N., Hu, G. L. & Zhang, Z. ( 2002; ). Helicobacter pylori cagA and vacA cytotoxin genes in Changsha, China. Br J Biomed Sci 59, 150–153.
    [Google Scholar]
  64. Yamaoka, Y., Kodama, T., Kashima, K., Graham, D. Y. & Sepulveda, A. R. ( 1998; ). Variants of the 3′ region of the cagA gene in Helicobacter pylori – associated diseases. J Clin Microbiol 36, 2258–2263.
    [Google Scholar]
  65. Zhang, Y., Argent, R. H., Letley, D. P., Thomas, R. J. & Atherton, J. C. ( 2005; ). Tyrosine phosphorylation of cagA from Chinese Helicobacter pylori isolates in AGS gastric epithelial cells. J Clin Microbiol 43, 786–790.[CrossRef]
    [Google Scholar]
  66. Zhou, J., Zhang, J., Xu, C. & He, L. ( 2004a; ). cagA genotype and variants in Chinese Helicobacter pylori strains and relationship to gastroduodenal diseases. J Med Microbiol 53, 231–235.[CrossRef]
    [Google Scholar]
  67. Zhou, W., Yamazaki, S., Yamakawa, A., Ohtani, M., Ito, Y., Keida, Y., Higashi, H., Hatakeyama, M., Si, J. & Azuma, T. ( 2004b; ). The diversity of vacA and cagA genes of Helicobacter pylori in East Asia. FEMS Immunol Med Microbiol 40, 81–87.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.2006/002923-0
Loading
/content/journal/micro/10.1099/mic.0.2006/002923-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error