Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1995 Jan;63(1):94–98. doi: 10.1128/iai.63.1.94-98.1995

Analysis of expression of CagA and VacA virulence factors in 43 strains of Helicobacter pylori reveals that clinical isolates can be divided into two major types and that CagA is not necessary for expression of the vacuolating cytotoxin.

Z Xiang 1, S Censini 1, P F Bayeli 1, J L Telford 1, N Figura 1, R Rappuoli 1, A Covacci 1
PMCID: PMC172962  PMID: 7806390

Abstract

Colonization of the mucosa of the stomach and the duodenum by Helicobacter pylori is the major cause of acute and chronic gastroduodenal pathologies in humans. Duodenal ulcer formation strongly correlates with the expression of an antigen (CagA) that is usually coeexpressed with the vacuolating cytotoxin (VacA), a protein that causes ulceration in the stomach of mice. However, the relationship between these two virulence factors is unknown. To define whether CagA and VacA are coexpressed in all clinical isolates and their relationships, we collected 43 clinical isolates of H. pylori and studied their genetic and phenotypic properties. Based on this analysis, most of the strains could be classified into two major types. Type I bacteria had the gene coding for CagA and expressed the CagA protein and the vacuolating cytotoxin. Type II bacteria did not have the gene coding for CagA and did not express either the CagA protein or the vacuolating cytotoxin. Type I and type II bacteria represented 56 and 16%, respectively, of the 43 clinical isolates, while the remaining 28% had an intermediate phenotype, expressing CagA independently of VacA or vice versa. This finding shows that although it is present in most cytotoxic strains, CagA is not necessary for the expression of the vacuolating cytotoxin.

Full Text

The Full Text of this article is available as a PDF (290.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blaser M. J. Helicobacter pylori and the pathogenesis of gastroduodenal inflammation. J Infect Dis. 1990 Apr;161(4):626–633. doi: 10.1093/infdis/161.4.626. [DOI] [PubMed] [Google Scholar]
  2. Blaser M. J. Helicobacter pylori: microbiology of a 'slow' bacterial infection. Trends Microbiol. 1993 Oct;1(7):255–260. doi: 10.1016/0966-842x(93)90047-u. [DOI] [PubMed] [Google Scholar]
  3. Borén T., Falk P., Roth K. A., Larson G., Normark S. Attachment of Helicobacter pylori to human gastric epithelium mediated by blood group antigens. Science. 1993 Dec 17;262(5141):1892–1895. doi: 10.1126/science.8018146. [DOI] [PubMed] [Google Scholar]
  4. Covacci A., Censini S., Bugnoli M., Petracca R., Burroni D., Macchia G., Massone A., Papini E., Xiang Z., Figura N. Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5791–5795. doi: 10.1073/pnas.90.12.5791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cover T. L., Dooley C. P., Blaser M. J. Characterization of and human serologic response to proteins in Helicobacter pylori broth culture supernatants with vacuolizing cytotoxin activity. Infect Immun. 1990 Mar;58(3):603–610. doi: 10.1128/iai.58.3.603-610.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cover T. L., Tummuru M. K., Cao P., Thompson S. A., Blaser M. J. Divergence of genetic sequences for the vacuolating cytotoxin among Helicobacter pylori strains. J Biol Chem. 1994 Apr 8;269(14):10566–10573. [PubMed] [Google Scholar]
  7. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  8. Labigne A., Cussac V., Courcoux P. Shuttle cloning and nucleotide sequences of Helicobacter pylori genes responsible for urease activity. J Bacteriol. 1991 Mar;173(6):1920–1931. doi: 10.1128/jb.173.6.1920-1931.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Leying H., Suerbaum S., Geis G., Haas R. Cloning and genetic characterization of a Helicobacter pylori flagellin gene. Mol Microbiol. 1992 Oct;6(19):2863–2874. doi: 10.1111/j.1365-2958.1992.tb01466.x. [DOI] [PubMed] [Google Scholar]
  10. Olivieri R., Bugnoli M., Armellini D., Bianciardi S., Rappuoli R., Bayeli P. F., Abate L., Esposito E., de Gregorio L., Aziz J. Growth of Helicobacter pylori in media containing cyclodextrins. J Clin Microbiol. 1993 Jan;31(1):160–162. doi: 10.1128/jcm.31.1.160-162.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Paster B. J., Lee A., Fox J. G., Dewhirst F. E., Tordoff L. A., Fraser G. J., O'Rourke J. L., Taylor N. S., Ferrero R. Phylogeny of Helicobacter felis sp. nov., Helicobacter mustelae, and related bacteria. Int J Syst Bacteriol. 1991 Jan;41(1):31–38. doi: 10.1099/00207713-41-1-31. [DOI] [PubMed] [Google Scholar]
  12. Phadnis S. H., Ilver D., Janzon L., Normark S., Westblom T. U. Pathological significance and molecular characterization of the vacuolating toxin gene of Helicobacter pylori. Infect Immun. 1994 May;62(5):1557–1565. doi: 10.1128/iai.62.5.1557-1565.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Schmitt W., Haas R. Genetic analysis of the Helicobacter pylori vacuolating cytotoxin: structural similarities with the IgA protease type of exported protein. Mol Microbiol. 1994 Apr;12(2):307–319. doi: 10.1111/j.1365-2958.1994.tb01019.x. [DOI] [PubMed] [Google Scholar]
  14. Spiegelhalder C., Gerstenecker B., Kersten A., Schiltz E., Kist M. Purification of Helicobacter pylori superoxide dismutase and cloning and sequencing of the gene. Infect Immun. 1993 Dec;61(12):5315–5325. doi: 10.1128/iai.61.12.5315-5325.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Stemmer W. P. A 20-minute ethidium bromide/high-salt extraction protocol for plasmid DNA. Biotechniques. 1991 Jun;10(6):726–726. [PubMed] [Google Scholar]
  16. Suerbaum S., Josenhans C., Labigne A. Cloning and genetic characterization of the Helicobacter pylori and Helicobacter mustelae flaB flagellin genes and construction of H. pylori flaA- and flaB-negative mutants by electroporation-mediated allelic exchange. J Bacteriol. 1993 Jun;175(11):3278–3288. doi: 10.1128/jb.175.11.3278-3288.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Telford J. L., Ghiara P., Dell'Orco M., Comanducci M., Burroni D., Bugnoli M., Tecce M. F., Censini S., Covacci A., Xiang Z. Gene structure of the Helicobacter pylori cytotoxin and evidence of its key role in gastric disease. J Exp Med. 1994 May 1;179(5):1653–1658. doi: 10.1084/jem.179.5.1653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Tummuru M. K., Cover T. L., Blaser M. J. Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: evidence of linkage to cytotoxin production. Infect Immun. 1993 May;61(5):1799–1809. doi: 10.1128/iai.61.5.1799-1809.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Tummuru M. K., Cover T. L., Blaser M. J. Mutation of the cytotoxin-associated cagA gene does not affect the vacuolating cytotoxin activity of Helicobacter pylori. Infect Immun. 1994 Jun;62(6):2609–2613. doi: 10.1128/iai.62.6.2609-2613.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Xiang Z., Bugnoli M., Ponzetto A., Morgando A., Figura N., Covacci A., Petracca R., Pennatini C., Censini S., Armellini D. Detection in an enzyme immunoassay of an immune response to a recombinant fragment of the 128 kilodalton protein (CagA) of Helicobacter pylori. Eur J Clin Microbiol Infect Dis. 1993 Oct;12(10):739–745. doi: 10.1007/BF02098460. [DOI] [PubMed] [Google Scholar]
  21. Xiang Z., Bugnoli M., Rappuoli R., Covacci A., Ponzetto A., Crabtree J. E. Helicobacter pylori: host responses in peptic ulceration. Lancet. 1993 Apr 3;341(8849):900–901. doi: 10.1016/0140-6736(93)93113-f. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES