1887

Abstract

Putative virulence genes of are generally classified into three categories: strain-specific genes, phase-variable genes and genes with variable structures/genotypes. Among these, there has recently been considerable interest in strain-specific genes found outside of the pathogenicity island, especially genes in the plasticity regions. Nearly half of the strain-specific genes of are located in the plasticity regions in strains 26695 and J99. Strain HPAG1, however, seems to lack a typical plasticity region; instead it has 43 HPAG1-specific genes which are either undetectable or incompletely represented in the genomes of strains 26695 and J99. Recent studies showed that certain genes or combination of genes in this region may play important roles in the pathogenesis of -associated gastroduodenal diseases. Most previous studies have focused on the plasticity region in strain J99 () and the gene and the uodenal lcer romoting () gene are good candidate markers for gastroduodenal diseases although there are some paradoxical findings. The gene is reported to be associated with an increased risk of both duodenal ulcers and gastric cancers, whereas the gene, which encompasses and , is reported to be associated with an increased risk of duodenal ulcers and protection against gastric cancers. In addition, recent studies showed that approximately 10–30 % of clinical isolates possess a 16.3 kb type IV secretion apparatus () in the plasticity region. Studies on the plasticity region have only just begun, and further investigation is necessary to elucidate the roles of genes in this region in gastroduodenal pathogenesis.

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2008-05-01
2024-10-03
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References

  1. Alm R. A., Trust T. J. 1999; Analysis of the genetic diversity of Helicobacter pylori : the tale of two genomes. J Mol Med 77:834–846 [CrossRef]
    [Google Scholar]
  2. 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]
  3. Arachchi H. S. J., Kalra V., Lal B., Bhatia V., Baba C. S., Chakravarthy S., Rohatgi S., Sarma P. M., Mishra V. other authors 2007; Prevalence of duodenal ulcer-promoting gene ( dupA ) of Helicobacter pylori in patients with duodenal ulcer in North Indian population. Helicobacter 12:591–597 [CrossRef]
    [Google Scholar]
  4. Argent R. H., Burette A., Miendje Deyi V. Y., Atherton J. C. 2007; The presence of dupA in Helicobacter pylori is not significantly associated with duodenal ulceration in Belgium, South Africa, China, or North America. Clin Infect Dis 45:1204–1206 [CrossRef]
    [Google Scholar]
  5. Asahi M., Azuma T., Ito S., Ito Y., Suto H., Nagai Y., Tsubokawa M., Tohyama Y., Maeda S. other authors 2000; Helicobacter pylori CagA protein can be tyrosine phosphorylated in gastric epithelial cells. J Exp Med 191:593–602 [CrossRef]
    [Google Scholar]
  6. Atherton J. C., Cao P., Peek R. M. Jr, Tummuru M. K., Blaser 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. Backert S., Ziska E., Brinkmann V., Zimny-Arndt U., Fauconnier A., Jungblut P. R., Naumann M., Meyer T. F. 2000; Translocation of the Helicobacter pylori CagA protein in gastric epithelial cells by a type IV secretion apparatus. Cell Microbiol 2:155–164 [CrossRef]
    [Google Scholar]
  8. 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]
  9. Buhrdorf R., Forster C., Haas R., Fischer W. 2003; Topological analysis of a putative virB8 homologue essential for the cag type IV secretion system in Helicobacter pylori . Int J Med Microbiol 293:213–217 [CrossRef]
    [Google Scholar]
  10. 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]
  11. Colbeck J. C., Hansen L. M., Fong J. M., Solnick J. V. 2006; Genotypic profile of the outer membrane proteins BabA and BabB in clinical isolates of Helicobacter pylori . Infect Immun 74:4375–4378 [CrossRef]
    [Google Scholar]
  12. Covacci A., Telford J. L., Del G. G., Parsonnet J., Rappuoli R. 1999; Helicobacter pylori virulence and genetic geography. Science 284:1328–1333 [CrossRef]
    [Google Scholar]
  13. de Jonge R., Kuipers E. J., Langeveld S. C., Loffeld R. J., Stoof J., van Vliet A. H., Kusters J. G. 2004; The Helicobacter pylori plasticity region locus jhp0947-jhp0949 is associated with duodenal ulcer disease and interleukin-12 production in monocyte cells. FEMS Immunol Med Microbiol 41:161–167 [CrossRef]
    [Google Scholar]
  14. Douraghi M., Mohammadi M., Oghalaie A., Abdirad A., Mohagheghi M. A., Eshagh Hosseini M., Zeraati H., Ghasemi A., Esmaieli M., Mohajerani N. 2008; dupA as a risk determinant in Helicobacter pylori infection. J Med Microbiol 57:554–562 [CrossRef]
    [Google Scholar]
  15. 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]
  16. Fischer W., Puls J., Buhrdorf R., Gebert B., Odenbreit S., Haas R. 2001; Systematic mutagenesis of the Helicobacter pylori cag pathogenicity island: essential genes for CagA translocation in host cells and induction of interleukin-8. Mol Microbiol 42:1337–1348
    [Google Scholar]
  17. Fujimoto S., Olaniyi O. O., Arnqvist A., Wu J. Y., Odenbreit S., Haas R., Graham D. Y., Yamaoka Y. 2007; Helicobacter pylori BabA expression, gastric mucosal injury, and clinical outcome. Clin Gastroenterol Hepatol 5:49–58 [CrossRef]
    [Google Scholar]
  18. Gerhard M., Lehn N., Neumayer N., Boren T., Rad R., Schepp W., Miehlke S., Classen M., Prinz C. 1999; Clinical relevance of the Helicobacter pylori gene for blood-group antigen-binding adhesin. Proc Natl Acad Sci U S A 96:12778–12783 [CrossRef]
    [Google Scholar]
  19. Glocker E., Lange C., Covacci A., Bereswill S., Kist M., Pahl H. L. 1998; Proteins encoded by the cag pathogenicity island of Helicobacter pylori are required for NF-kappaB activation. Infect Immun 66:2346–2348
    [Google Scholar]
  20. Gomes L. I., Rocha G. A., Rocha A. M., Soares T. F., Oliveira C. A., Bittencourt P. F., Queiroz D. M. 2008; Lack of association between Helicobacter pylori infection with dupA -positive strains and gastroduodenal diseases in Brazilian patients. Int J Med Microbiol in press
    [Google Scholar]
  21. 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 Genet 1:e43 [CrossRef]
    [Google Scholar]
  22. Hennig E. E., Allen J. M., Cover T. L. 2006; Multiple chromosomal loci for the babA gene in Helicobacter pylori . Infect Immun 74:3046–3051 [CrossRef]
    [Google Scholar]
  23. Hofreuter D., Odenbreit S., Henke G., Haas R. 1998; Natural competence for DNA transformation in Helicobacter pylori : identification and genetic characterization of the comB locus. Mol Microbiol 28:1027–1038 [CrossRef]
    [Google Scholar]
  24. Hofreuter D., Odenbreit S., Haas R. 2001; Natural transformation competence in Helicobacter pylori is mediated by the basic components of a type IV secretion system. Mol Microbiol 41:379–391 [CrossRef]
    [Google Scholar]
  25. Kersulyte D., Velapatino B., Mukhopadhyay A. K., Cahuayme L., Bussalleu A., Combe J., Gilman R. H., Berg D. E. 2003; Cluster of type IV secretion genes in Helicobacter pylori' s plasticity zone. J Bacteriol 185:3764–3772 [CrossRef]
    [Google Scholar]
  26. Lehours P., Dupouy S., Bergey B., Ruskoné-Foumestraux A., Delchier J. C., Rad R., Richy F., Tankovic J., Zerbib F. other authors 2004; Identification of a genetic marker of Helicobacter pylori strains involved in gastric extranodal marginal zone B cell lymphoma of the MALT-type. Gut 53:931–937 [CrossRef]
    [Google Scholar]
  27. Linz B., Balloux F., Moodley Y., Manica A., Liu H., Roumagnac P., Falush D., Stamer C., Prugnolle F. other authors 2007; An African origin for the intimate association between humans and Helicobacter pylori . Nature 445:915–918 [CrossRef]
    [Google Scholar]
  28. Lu H., Hsu P. I., Graham D. Y., Yamaoka Y. 2005a; Duodenal ulcer promoting gene of Helicobacter pylori . Gastroenterology 128:833–848 [CrossRef]
    [Google Scholar]
  29. Lu H., Yamaoka Y., Graham D. Y. 2005b; Helicobacter pylori virulence factors: facts and fantasies. Curr Opin Gastroenterol 21:653–659 [CrossRef]
    [Google Scholar]
  30. Lu H., Wu J. Y., Beswick E. J., Ohno T., Odenbreit S., Haas R., Reyes V. E., Kita M., Graham D. Y., Yamaoka Y. 2007; Functional and intracellular signaling differences associated with the Helicobacter pylori AlpAB adhesin from Western and East Asian strains. J Biol Chem 282:6242–6254
    [Google Scholar]
  31. Occhialini A., Marais A., Alm R., Garcia F., Sierra R., Megraud F. 2000; Distribution of open reading frames of plasticity region of strain J99 in Helicobacter pylori strains isolated from gastric carcinoma and gastritis patients in Costa Rica. Infect Immun 68:6240–6249 [CrossRef]
    [Google Scholar]
  32. Odenbreit S., Puls J., Sedlmaier B., Gerland E., Fischer W., Haas R. 2000; Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science 287:1497–1500 [CrossRef]
    [Google Scholar]
  33. Oh J. D., Kling-Backhed H., Giannakis M., Xu J., Fulton R. S., Fulton L. A., Cordum H. S., Wang C., Elliott G. other authors 2006; The complete genome sequence of a chronic atrophic gastritis Helicobacter pylori strain: evolution during disease progression. Proc Natl Acad Sci U S A 103:9999–10004 [CrossRef]
    [Google Scholar]
  34. Rizwan M., Alvi A., Ahmed N. 2008; Novel protein antigen (JHP940) from the genomic plasticity region of Helicobacter pylori induces TNF-alpha and interleukin-8 secretion by human macrophages. J Bacteriol 190:1146–1151 [CrossRef]
    [Google Scholar]
  35. Salama N. R., Guillemin K., McDaniel T. K., Sherlock G., Tompkins L., Falkow S. 2000; A whole-genome microarray reveals genetic diversity among Helicobacter pylori strains. Proc Natl Acad Sci U S A 97:14668–14673 [CrossRef]
    [Google Scholar]
  36. Salih B. A., Abasiyanik M. F., Ahmed N. 2007; A preliminary study on the genetic profile of cag pathogenicity-island and other virulent gene loci of Helicobacter pylori strains from Turkey. Infect Genet Evol 7:509–512 [CrossRef]
    [Google Scholar]
  37. Santos A., Queiroz D. M., Menard A., Marais A., Rocha G. A., Oliveira C. A., Nogueira A. M., Uzeda M., Megraud F. 2003; New pathogenicity marker found in the plasticity region of the Helicobacter pylori genome. J Clin Microbiol 41:1651–1655 [CrossRef]
    [Google Scholar]
  38. Segal E. D., Cha J., Lo J., Falkow S., Tompkins L. S. 1999; Altered states: involvement of phosphorylated CagA in the induction of host cellular growth changes by Helicobacter pylori . Proc Natl Acad Sci U S A 96:14559–14564 [CrossRef]
    [Google Scholar]
  39. Selbach M., Moese S., Meyer T. F., Backert S. 2002; Functional analysis of the Helicobacter pylori cag pathogenicity island reveals both VirD4-CagA-dependent and VirD4-CagA-independent mechanisms. Infect Immun 70:665–671 [CrossRef]
    [Google Scholar]
  40. Smeets L. C., Kusters J. G. 2002; Natural transformation in Helicobacter pylori : DNA transport in an unexpected way. Trends Microbiol 10:159–162 [CrossRef]
    [Google Scholar]
  41. Stein M., Rappuoli R., Covacci A. 2000; Tyrosine phosphorylation of the Helicobacter pylori CagA antigen after cag-driven host cell translocation. Proc Natl Acad Sci U S A 97:1263–1268 [CrossRef]
    [Google Scholar]
  42. Tanaka J., Suzuki T., Mimuro H., Sasakawa C. 2003; Structural definition on the surface of Helicobacter pylori type IV secretion apparatus. Cell Microbiol 5:395–404 [CrossRef]
    [Google Scholar]
  43. 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]
  44. van Doorn L. J., Figueiredo C., Sanna R., Plaisier A., Schneeberger P., de Boer W., Quint W. 1998; Clinical relevance of the cagA , vacA , and iceA status of Helicobacter pylori . Gastroenterology 115:58–66 [CrossRef]
    [Google Scholar]
  45. 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]
  46. Yamaoka Y., Kita M., Kodama T., Sawai N., Tanahashi T., Kashima K., Imanishi J. 1998a; Chemokines in the gastric mucosa in Helicobacter pylori infection. Gut 42:609–617 [CrossRef]
    [Google Scholar]
  47. Yamaoka Y., Kodama T., Kashima K., Graham D. Y., Sepulveda A. R. 1998b; 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]
  48. Yamaoka Y., El-Zimaity H. M., Gutierrez O., Figura N., Kim J. G., Kodama T., Kashima K., Graham D. Y. 1999a; Relationship between the cagA 3′ repeat region of Helicobacter pylori , gastric histology, and susceptibility to low pH. Gastroenterology 117:342–349 [CrossRef]
    [Google Scholar]
  49. Yamaoka Y., Kodama T., Kita M., Imanishi J., Kashima K., Graham D. Y. 1999b; Relation between clinical presentation, Helicobacter pylori density, interleukin 1beta and 8 production, and cagA status. Gut 45:804–811 [CrossRef]
    [Google Scholar]
  50. Yamaoka Y., Kikuchi S., El-Zimaity H. M., Gutierrez O., Osato M. S., Graham D. Y. 2002; Importance of Helicobacter pylori oipA in clinical presentation, gastric inflammation, and mucosal interleukin 8 production. Gastroenterology 123:414–424 [CrossRef]
    [Google Scholar]
  51. Yamaoka Y., Ojo O., Fujimoto S., Odenbreit S., Haas R., Gutierrez O., El-Zimaity H. M., Reddy R., Arnqvist A., Graham D. Y. 2006; Helicobacter pylori outer membrane proteins and gastroduodenal disease. Gut 55:775–781 [CrossRef]
    [Google Scholar]
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