1887

Abstract

strains from East Asia have an ‘East Asian’ type of CagA that is more active and predominantly comprises a single type. Strains from other countries have a ‘western’ type of CagA, which is less active and comprises many different types generated by intragenomic recombination. Co-culture of AGS gastric epithelial cells with isolates of western strains that displayed microevolution in CagA showed that isolates with additional copies of the C motif induced significantly more interleukin (IL)-8 secretion. Co-culture of AGS cells with western and East Asian strains, each expressing CagA with a single copy of the C or D motif, showed that East Asian strains induced significantly more IL-8 secretion. Analysis of the different CagA types from data deposited in GenBank and from the literature showed that western CagA is significantly more likely to undergo duplication of tyrosine phosphorylation motif C than East Asian CagA is of the corresponding D motif. Taken together, the data suggest that the already highly active East Asian CagA with one D motif has no requirement to increase its virulence, whereas the less active western CagA displays flexibility in its capacity to increase its number of tyrosine phosphorylation motifs to become more virulent.

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2008-09-01
2024-11-06
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References

  1. Akopyanz N., Bukanov N. O., Westblom T. U., Kresovich S., Berg D. E. 1992; DNA diversity among clinical isolates of Helicobacter pylori detected by DNA-based RAPD fingerprinting. Nucleic Acids Res 20:5137–5142 [CrossRef]
    [Google Scholar]
  2. Aras R. A., Lee Y., Kim S.-K., Israel D., Peek R. M. Jr, Blaser M. J. 2003; Natural variation in populations of persistently colonizing bacteria affect human host cell phenotype. J Infect Dis 188:486–496 [CrossRef]
    [Google Scholar]
  3. Argent R. H., Kidd M., Owen R. J., Thomas R. J., Limb M. C., Atherton J. C. 2004; Determinants and consequences of different levels of CagA phosphorylation for clinical isolates of Helicobacter pylori . Gastroenterology 127:514–523 [CrossRef]
    [Google Scholar]
  4. Argent R. H., Zhang Y., Atherton J. C. 2005; Simple method for determination of the number of Helicobacter pylori CagA variable-region EPIYA tyrosine phosphorylation motifs by PCR. J Clin Microbiol 43:791–795 [CrossRef]
    [Google Scholar]
  5. Argent R. H., Thomas R. J., Aviles-Jimenez J., Letley D. P., Limb M. C., El-Omar E. M., Atherton J. C. 2008a; Toxigenic Helicobacter pylori infection precedes gastric hypochlorhydria in cancer relatives, and H. pylori virulence evolves in these families. Clin Cancer Res 14:2227–2235 [CrossRef]
    [Google Scholar]
  6. Argent R. H., Thomas R. J., Letley D. P., Rittig M. G., Hardie K. R., Atherton J. C. 2008b; Functional association between the Helicobacter pylori virulence factors VacA and CagA. J Med Microbiol 57:145–150 [CrossRef]
    [Google Scholar]
  7. Atherton J. C. 2006; The pathogenesis of Helicobacter pylori -induced gastro-duodenal diseases. Annu Rev Pathol Mech Dis 1:63–96 [CrossRef]
    [Google Scholar]
  8. Azuma T., Yamazaki S., Yamakawa A., Ohtani M., Muramatsu A., Suto H., Ito Y., Dojo M., Yamazaki Y. other authors 2004; Association between diversity in the Src homology 2 domain-containing tyrosine phosphatase binding site of Helicobacter pylori CagA protein and gastric atrophy and cancer. J Infect Dis 189:820–827 [CrossRef]
    [Google Scholar]
  9. Blaser M. J., Perez-Perez G. I., Kleanthous H., Cover T. L., Peek R. M., Chyou P. H., Stemmermann G. N., Nomura A. 1995; Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res 55:2111–2115
    [Google Scholar]
  10. Brandt S., Kwok T., Hartig R., König W., Backert S. 2005; NF- κ B activation and potentiation of proinflammatory responses by the Helicobacter pylori CagA protein. Proc Natl Acad Sci U S A 102:9300–9305 [CrossRef]
    [Google Scholar]
  11. Carroll I. M., Ahmed N., Beesley S. M., Khan A. A., Ghousunnissa S., Moráin C. A. O., Habibullah C. M., Smyth C. J. 2004; Microevolution between paired antrum and corpus Helicobacter pylori isolates recovered from individual patients. J Med Microbiol 53:669–677 [CrossRef]
    [Google Scholar]
  12. Censini S., Lange C., Xiang Z., Crabtree J. E., Ghiara P., Borodovsky M., Rappuoli R., Covacci A. 1996; cag , a pathogenicity island of Helicobacter pylori , encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci U S A 93:14648–14653 [CrossRef]
    [Google Scholar]
  13. Choi K. D., Kim N., Lee D. H., Kim J. M., Kim J. S., Jung H. C., Song I. S. 2007; Analysis of the 3′ variable region of the cagA gene of Helicobacter pylori isolated in Koreans. Dig Dis Sci 52:960–966 [CrossRef]
    [Google Scholar]
  14. Covacci A., Censini S., Bugnoli M., Petracca R., Burroni D., Macchia G., Massone A., Papini E., Xiang Z. other authors 1993; Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulceration. Proc Natl Acad Sci U S A 90:5791–5795 [CrossRef]
    [Google Scholar]
  15. De Sousa D., Fabri L. J., Nash A., Hilton D. J., Nicola N. A., Baca M. 2002; SH2 domains from suppressor of cytokine signaling-3 and protein tyrosine phosphatase SHP-2 have similar binding specificities. Biochemistry 41:9229–9236 [CrossRef]
    [Google Scholar]
  16. Devi S. M., Ahmed I., Khan A. A., Rahman S. A., Alvi A., Sechi L. A., Ahmed N. 2006; Genomes of Helicobacter pylori from native Peruvians suggest admixture of ancestral and modern lineages and reveal a western type cag -pathogenicity island. BMC Genomics 7:191 [CrossRef]
    [Google Scholar]
  17. Dong Q., O'Sullivan M., Hall W., Herra C., Kean C., O'Morain C., Buckley M. 2002; Identification of a new segment involved in cagA 3′ region variation of Helicobacter pylori . FEMS Immunol Med Microbiol 33:51–55
    [Google Scholar]
  18. El-Omar E. M., Carrington M., Chow W.-H., McColl K. E. L., Bream J. H., Young H. A., Herrera J., Lissowska J., Yuan C.-C. other authors 2000a; Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 404:398–402 [CrossRef]
    [Google Scholar]
  19. El-Omar E. M., Oien K., Murray L. S., El-Nujumi A., Wirz A., Gillen D., Williams C., Fullarton G., McColl K. E. L. 2000b; Increased prevalence of precancerous changes in relatives of gastric cancer patients: critical role of H. pylori . Gastroenterology 118:22–30 [CrossRef]
    [Google Scholar]
  20. Evans D. J. Jr, Quieroz D. M. M., Mendes E. N., Evans D. G. 1998; Diversity in the variable region of Helicobacter pylori cagA gene involves more than simple repetition of a 102-nucleotide sequence. Biochem Biophys Res Commun 245:780–784 [CrossRef]
    [Google Scholar]
  21. Hatakeyama M. 2006; Helicobacter pylori CagA – a bacterial intruder conspiring gastric carcinogenesis. Int J Cancer 119:1217–1223 [CrossRef]
    [Google Scholar]
  22. Higashi H., Tsutsumi R., Fujita A., Yamazaki S., Asaka M., Azuma T., Hatakeyama M. 2002a; Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. Proc Natl Acad Sci U S A 99:14428–14433 [CrossRef]
    [Google Scholar]
  23. Higashi H., Tsutsumi R., Muto S., Sugiyama T., Azuma T., Asaka M., Hatakeyama M. 2002b; SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Protein Sci 295:683–686
    [Google Scholar]
  24. Higashi H., Nakaya A., Tsutsumi R., Yokoyama K., Fujii Y., Ishikawa S., Higuchi M., Takahashi A., Kurashima Y. other authors 2004; Helicobacter pylori CagA induces Ras-independent morphogenetic response through SHP-2 recruitment and activation. J Biol Chem 279:17205–17216 [CrossRef]
    [Google Scholar]
  25. Keates S., Hitti Y. S., Upton M., Kelly C. P. 1997; Helicobacter pylori infection activates NF- κ B in gastric epithelial cells. Gastroenterology 113:1099–1109 [CrossRef]
    [Google Scholar]
  26. Kim S.-Y., Lee Y.-C., Kim H. K., Blaser M. J. 2006; Helicobacter pylori CagA transfection of gastric epithelial cells induces interleukin-8. Cell Microbiol 8:97–106 [CrossRef]
    [Google Scholar]
  27. Naito M., Yamazaki T., Tsutsumi R., Higashi H., Onoe K., Yamazaki S., Azuma T., Hatakeyama M. 2006; Influence of EPIYA-repeat polymorphism on the phosphorylation-dependent biological activity of Helicobacter pylori CagA. Gastroenterology 130:1181–1190 [CrossRef]
    [Google Scholar]
  28. Panayotopoulou E. G., Sgouras D. N., Papadakos K., Kalliaropoulos A., Papatheodoridis G., Mentis A. F., Archimandritis A. J. 2007; Strategy to characterize the number and type of repeating EPIYA phosphorylation motifs in the carboxy terminus of CagA protein in Helicobacter pylori clinical isolates. J Clin Microbiol 45:488–495 [CrossRef]
    [Google Scholar]
  29. Poppe M., Feller S. M., Römer G., Wessler S. 2007; Phosphorylation of Helicobacter pylori CagA by c-Abl leads to cell motility. Oncogene 26:3462–3472 [CrossRef]
    [Google Scholar]
  30. Reyes-Leon A., Atherton J. C., Argent R. H., Puente J. L., Torres J. 2007; Heterogeneity in the activity of Mexican Helicobacter pylori strains in gastric epithelial cells and its association with diversity in the cagA gene. Infect Immun 75:3445–3454 [CrossRef]
    [Google Scholar]
  31. Robinson K., Argent R. H., Atherton J. C. 2007; The inflammatory and immune response to Helicobacter pylori infection. Best Pract Res Clin Gastroenterol 21:237–259 [CrossRef]
    [Google Scholar]
  32. Rudi J., Kolb C., Maiwald M., Zuna I., von Herbay A., Galle P. R., Stremmel W. 1998; Diversity of Helicobacter pylori vacA and cagA genes and relationship to VacA and CagA protein expression, cytotoxin production, and associated diseases. J Clin Microbiol 36:944–948
    [Google Scholar]
  33. Selbach M., Moese S., Hauck C. R., Meyer T. F., Backert S. 2002; Src is the kinase of the Helicobacter pylori CagA protein in vitro and in vivo . J Biol Chem 277:6775–6778 [CrossRef]
    [Google Scholar]
  34. Stein M., Bagnoli F., Halenbeck R., Rappuoli R., Fantl W. J., Covacci A. 2002; c-Src/Lyn kinases activate Helicobacter pylori CagA through tyrosine phosphorylation of the EPIYA motifs. Mol Microbiol 43:971–980 [CrossRef]
    [Google Scholar]
  35. Tammer I., Brandt S., Hartig R., König W., Backert S. 2007; Activation of Abl by Helicobacter pylori : a novel kinase for CagA and crucial mediator of host cell scattering. Gastroenterology 132:1309–1319 [CrossRef]
    [Google Scholar]
  36. Tsutsumi R., Higashi H., Higuchi M., Okada M., Hatakeyama M. 2003; Attenuation of Helicobacter pylori CagA·SHP-2 signaling by interaction between CagA and C-terminal Src kinase. J Biol Chem 278:3664–3670 [CrossRef]
    [Google Scholar]
  37. Tummuru M. K., Cover T. L., Blaser M. J. 1993; Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori : evidence of linkage to cytotoxin production. Infect Immun 61:1799–1809
    [Google Scholar]
  38. Tummuru M. K., Sharma S. A., Blaser M. J. 1995; Helicobacter pylori picB , a homologue of the Bordetella pertussis toxin secretion protein, is required for induction of IL-8 in gastric epithelial cells. Mol Microbiol 18:867–876 [CrossRef]
    [Google Scholar]
  39. Viala J., Chaput C., Boneca I. G., Cardona A., Girardin S. E., Moran A. P., Athman R., Mémet S., Huerre M. R. other authors 2004; Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nat Immunol 5:1166–1174 [CrossRef]
    [Google Scholar]
  40. 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 isolates from patients with different H. pylori -associated diseases. J Clin Microbiol 36:2258–2263
    [Google Scholar]
  41. 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]
  42. Zhu Y.-L., Zheng S., Du Q., Qian K.-D., Fang P.-C. 2005; Characterization of CagA variable region of Helicobacter pylori isolates from Chinese patients. World J Gastroenterol 11:880–884 [CrossRef]
    [Google Scholar]
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