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cagA  -  cag island protein, cytotoxicity...

Helicobacter pylori J99

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Disease relevance of cagA


High impact information on cagA

  • METHODS: Genotypic variations in virulence-associated genes of H. pylori vacA (s and m regions) and cagA were determined in 221 subjects with chronic gastritis and 222 patients with gastric carcinoma by polymerase chain reaction (PCR)-line probe assay [5].
  • Re: Helicobacter pylori and atrophic gastritis: importance of the cagA status [6].
  • One of the initially atrophy-negative, cagA-positive subjects developed early gastric cancer [7].
  • H. pylori strains can differ with respect to the presence of cagA (cytotoxin-associated gene A), a gene encoding a high-molecular-weight immunodominant antigen [7].
  • In six of these 16 subjects (five cagA positive versus one cagA negative), atrophic gastritis was accompanied by the development of intestinal metaplasia (i.e., a change in the type of specialized cells present) (P = .02; Fisher's exact test; RR = 9.06; 95% CI = 1.16-71.0) [7].

Chemical compound and disease context of cagA


Biological context of cagA

  • The cagA gene product CagA is injected into gastric epithelial cells, where it undergoes tyrosine phosphorylation by Src family kinases [1].
  • The vacA s1a genotype was detected in 66.7, 96.4, and 87.9% of isolates from patients with NUD, DU, and GC, respectively, and its presence was significantly associated with that of DU (p = .004), GC (p = .043), and cagA gene (p = .021) [13].
  • The coccoid H pylori contain completed cagA gene, which may be related to pathogenicity of them [14].
  • CONCLUSION: The recombinant plasmid containing cagA gene from coccoid H pylori has been constructed successfully [14].
  • RESULTS: cagA gene of 3,444 bp was obtained from the coccoid H pylori genome DNA [14].

Anatomical context of cagA

  • The aim of this study was to investigate the relationship between cagA gene and cytokine messenger RNA (mRNA) expression in gastric mucosa [15].
  • Active duodenitis was present only in patients with DU infected by cagA positive strains in the duodenum [16].
  • RESULTS: B128-infected gerbils harbored high numbers of bacteria in the gastric antrum and corpus, whereas B128delta cagY and B128delta cagA colonized the antrum more densely than the corpus [17].
  • Gastric cancer at the cardia is not associated with H. pylori infection or cagA -positive strains of H. pylori [18].
  • The cagA gene product CagA is delivered into gastric epithelial cells where it localizes to the plasma membrane and undergoes tyrosine phosphorylation at the EPIYA-repeat region, which contains the EPIYA-A segment, EPIYA-B segment, and Western CagA-specific EPIYA-C or East Asian CagA-specific EPIYA-D segment [19].

Associations of cagA with chemical compounds

  • In patients without atrophy, those infected with cagA+ had significantly higher (P = 0.03) PGE2 levels (53 +/- 1.1) than HP- patients (22.6 +/- 1.1) and greater levels (P = 0.29) than cagA- patients (35 +/- 1.3) [8].
  • Although there was no significant association between 23S rDNA mutations and the vacA and cagA status, clarithromycin-susceptible strains more often contained mixed vacA genotypes, indicating the presence of multiple H. pylori strains [20].
  • Southern hybridization of kanamycin-resistant H. pylori transformants demonstrated that the wild-type cagA gene had been disrupted by insertion of the kanamycin cassette, and immunoblot analysis showed that the mutant strains no longer produced the 128-kDa CagA protein [21].
  • Expression of XylE after growth in broth culture revealed that basal levels of expression of cagA and urea in H. pylori were substantially greater than for picB [22].
  • The cagA-negative H. pylori strains showed cytotoxin, urease, and phospholipase C activities, C3 binding and adherence similar to those of the isogenic wild-type strains [21].

Other interactions of cagA

  • The presence of vacA alleles, cagA, cagE, iceA, and babA2 genotypes were determined by polymerase chain reaction (PCR) [13].
  • Therefore, the aim of this study was to investigate the status of H. pylori strains regarding the babA and iceA alleles, as well as the cagA genotype, to reveal any association between these genotypes and clinical outcomes in Brazilian patients [23].
  • The number of nonsynonymous substitutions was much higher in cagA than in glmM, indicating positive selection [24].
  • Translocation of CagA was dependent on functional cagA gene and virulence (vir) genes of a type IV secretion apparatus composed of virB4, virB7, virB10, virB11 and virD4 encoded in the cag PAI of H. pylori [25].
  • Included in the list of regulated factors were the known virulence genes cagA, vacA, and napA [26].

Analytical, diagnostic and therapeutic context of cagA


  1. Functional antagonism between Helicobacter pylori CagA and vacuolating toxin VacA in control of the NFAT signaling pathway in gastric epithelial cells. Yokoyama, K., Higashi, H., Ishikawa, S., Fujii, Y., Kondo, S., Kato, H., Azuma, T., Wada, A., Hirayama, T., Aburatani, H., Hatakeyama, M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  2. EPIYA motif is a membrane-targeting signal of Helicobacter pylori virulence factor CagA in mammalian cells. Higashi, H., Yokoyama, K., Fujii, Y., Ren, S., Yuasa, H., Saadat, I., Murata-Kamiya, N., Azuma, T., Hatakeyama, M. J. Biol. Chem. (2005) [Pubmed]
  3. Transformed immortalized gastric epithelial cells by virulence factor CagA of Helicobacter pylori through Erk mitogen-activated protein kinase pathway. Zhu, Y., Zhong, X., Zheng, S., Du, Q., Xu, W. Oncogene (2005) [Pubmed]
  4. Functional variability of cagA gene in Japanese isolates of Helicobacter pylori. Hirata, Y., Yanai, A., Shibata, W., Mitsuno, Y., Maeda, S., Ogura, K., Yoshida, H., Kawabe, T., Omata, M. Gene (2004) [Pubmed]
  5. Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma. Figueiredo, C., Machado, J.C., Pharoah, P., Seruca, R., Sousa, S., Carvalho, R., Capelinha, A.F., Quint, W., Caldas, C., van Doorn, L.J., Carneiro, F., Sobrinho-Simões, M. J. Natl. Cancer Inst. (2002) [Pubmed]
  6. Re: Helicobacter pylori and atrophic gastritis: importance of the cagA status. Ponzetto, A., DeGiuli, M., Sanseverino, P., Soldati, T., Bazzoli, F. J. Natl. Cancer Inst. (1996) [Pubmed]
  7. Helicobacter pylori and atrophic gastritis: importance of the cagA status. Kuipers, E.J., Pérez-Pérez, G.I., Meuwissen, S.G., Blaser, M.J. J. Natl. Cancer Inst. (1995) [Pubmed]
  8. cagA+ Helicobacter pylori induces greater levels of prostaglandin E2 than cagA- strains. Al-Marhoon, M.S., Nunn, S., Soames, R.W. Prostaglandins Other Lipid Mediat. (2004) [Pubmed]
  9. Identification of cagA tyrosine phosphorylation DNA motifs in Helicobacter pylori isolates from peptic ulcer patients by novel PCR-restriction fragment length polymorphism and real-time fluorescence PCR assays. Owen, R.J., Sharp, S.I., Chisholm, S.A., Rijpkema, S. J. Clin. Microbiol. (2003) [Pubmed]
  10. Evaluation of clarithromycin resistance and cagA and vacA genotyping of Helicobacter pylori strains from the west of Ireland using line probe assays. Ryan, K.A., van Doorn, L.J., Moran, A.P., Glennon, M., Smith, T., Maher, M. J. Clin. Microbiol. (2001) [Pubmed]
  11. The phenotype of gastric mucosa coexisting with Barrett's oesophagus. Rugge, M., Russo, V., Busatto, G., Genta, R.M., Di Mario, F., Farinati, F., Graham, D.Y. J. Clin. Pathol. (2001) [Pubmed]
  12. Analysis of the 3' Variable Region of the cagA Gene of Helicobacter pylori Isolated in Koreans. Choi, K.D., Kim, N., Lee, D.H., Kim, J.M., Kim, J.S., Jung, H.C., Song, I.S. Dig. Dis. Sci. (2007) [Pubmed]
  13. Prevalence of Helicobacter pylori vacA, cagA, cagE, iceA, babA2 Genotypes and Correlation with Clinical Outcome in Turkish Patients with Dyspepsia. Erzin, Y., Koksal, V., Altun, S., Dobrucali, A., Aslan, M., Erdamar, S., Dirican, A., Kocazeybek, B. Helicobacter (2006) [Pubmed]
  14. Cloning and sequencing of cagA gene fragment of Helicobacter pylori with coccoid form. Wang, K.X., Wang, X.F. World J. Gastroenterol. (2004) [Pubmed]
  15. Helicobacter pylori cagA gene and expression of cytokine messenger RNA in gastric mucosa. Yamaoka, Y., Kita, M., Kodama, T., Sawai, N., Imanishi, J. Gastroenterology (1996) [Pubmed]
  16. Duodenal Helicobacter pylori infection differs in cagA genotype between asymptomatic subjects and patients with duodenal ulcers. Hamlet, A., Thoreson, A.C., Nilsson, O., Svennerholm, A.M., Olbe, L. Gastroenterology (1999) [Pubmed]
  17. Helicobacter pylori cag-type IV secretion system facilitates corpus colonization to induce precancerous conditions in Mongolian gerbils. Rieder, G., Merchant, J.L., Haas, R. Gastroenterology (2005) [Pubmed]
  18. Meta-analysis of the relationship between cagA seropositivity and gastric cancer. Huang, J.Q., Zheng, G.F., Sumanac, K., Irvine, E.J., Hunt, R.H. Gastroenterology (2003) [Pubmed]
  19. Structural Basis and Functional Consequence of Helicobacter pylori CagA Multimerization in Cells. Ren, S., Higashi, H., Lu, H., Azuma, T., Hatakeyama, M. J. Biol. Chem. (2006) [Pubmed]
  20. Accurate prediction of macrolide resistance in Helicobacter pylori by a PCR line probe assay for detection of mutations in the 23S rRNA gene: multicenter validation study. van Doorn, L.J., Glupczynski, Y., Kusters, J.G., Mégraud, F., Midolo, P., Maggi-Solcà, N., Queiroz, D.M., Nouhan, N., Stet, E., Quint, W.G. Antimicrob. Agents Chemother. (2001) [Pubmed]
  21. Mutation of the cytotoxin-associated cagA gene does not affect the vacuolating cytotoxin activity of Helicobacter pylori. Tummuru, M.K., Cover, T.L., Blaser, M.J. Infect. Immun. (1994) [Pubmed]
  22. Effect of growth phase and acid shock on Helicobacter pylori cagA expression. Karita, M., Tummuru, M.K., Wirth, H.P., Blaser, M.J. Infect. Immun. (1996) [Pubmed]
  23. Prevalence of Helicobacter pylori cagA, iceA and babA2 alleles in Brazilian patients with upper gastrointestinal diseases. Gatti, L.L., Módena, J.L., Payão, S.L., Smith, M.d.e. .A., Fukuhara, Y., Módena, J.L., de Oliveira, R.B., Brocchi, M. Acta Trop. (2006) [Pubmed]
  24. cagA-positive Helicobacter pylori populations in China and The Netherlands are distinct. van der Ende, A., Pan, Z.J., Bart, A., van der Hulst, R.W., Feller, M., Xiao, S.D., Tytgat, G.N., Dankert, J. Infect. Immun. (1998) [Pubmed]
  25. Translocation of the Helicobacter pylori CagA protein in gastric epithelial cells by a type IV secretion apparatus. Backert, S., Ziska, E., Brinkmann, V., Zimny-Arndt, U., Fauconnier, A., Jungblut, P.R., Naumann, M., Meyer, T.F. Cell. Microbiol. (2000) [Pubmed]
  26. Growth phase-dependent response of Helicobacter pylori to iron starvation. Merrell, D.S., Thompson, L.J., Kim, C.C., Mitchell, H., Tompkins, L.S., Lee, A., Falkow, S. Infect. Immun. (2003) [Pubmed]
  27. Biological activity of the virulence factor cagA of Helicobacter pylori. Zhu, Y.L., Zheng, S., Qian, K.D., Fang, P.C. Chin. Med. J. (2004) [Pubmed]
  28. Heterogeneous Helicobacter pylori isolates from members of a family with a history of peptic ulcer disease. van der Ende, A., Rauws, E.A., Feller, M., Mulder, C.J., Tytgat, G.N., Dankert, J. Gastroenterology (1996) [Pubmed]
  29. Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Blaser, M.J., Perez-Perez, G.I., Kleanthous, H., Cover, T.L., Peek, R.M., Chyou, P.H., Stemmermann, G.N., Nomura, A. Cancer Res. (1995) [Pubmed]
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