Skip to main content
NCBI home page
Journal of Bacteriology logoLink to Journal of Bacteriology
. 1997 May;179(9):2852–2856. doi: 10.1128/jb.179.9.2852-2856.1997

High-level genetic diversity in the vapD chromosomal region of Helicobacter pylori.

P Cao 1, T L Cover 1
PMCID: PMC179045  PMID: 9139899

Abstract

Helicobacter pylori isolates from different patients are characterized by diversity in the nucleotide sequences of individual genes, variation in genome size, and variation in gene order. Genetic diversity is particularly striking in vacuolating cytotoxin (vacA) alleles. In this study, five open reading frames (ORFs) were identified within a 4.2-kb region downstream from vacA in H. pylori 60190. One of these ORFs was closely related to the virulence-associated protein D (vapD) gene of Dichelobacter nodosus (64.9% nucleotide identity). A probe derived from vapD of H. pylori 60190 hybridized with only 19 (61.3%) of 31 H. pylori strains tested. Sequence analysis of the vapD region in vapD-negative H. pylori strains revealed that there were two different families of approximately 0.5-kb DNA segments, which were both unrelated to vapD. The presence of vapD was not associated with any specific family of vacA alleles. These findings are consistent with a recombinational population structure for H. pylori.

Full Text

The Full Text of this article is available as a PDF (214.9 KB).

Selected References

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

  1. Akopyanz N., Bukanov N. O., Westblom T. U., Berg D. E. PCR-based RFLP analysis of DNA sequence diversity in the gastric pathogen Helicobacter pylori. Nucleic Acids Res. 1992 Dec 11;20(23):6221–6225. doi: 10.1093/nar/20.23.6221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Akopyanz N., Bukanov N. O., Westblom T. U., Kresovich S., Berg D. E. DNA diversity among clinical isolates of Helicobacter pylori detected by PCR-based RAPD fingerprinting. Nucleic Acids Res. 1992 Oct 11;20(19):5137–5142. doi: 10.1093/nar/20.19.5137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Atherton J. C., Cao P., Peek R. M., Jr, Tummuru M. K., Blaser M. J., Cover T. L. Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem. 1995 Jul 28;270(30):17771–17777. doi: 10.1074/jbc.270.30.17771. [DOI] [PubMed] [Google Scholar]
  4. Billington S. J., Johnston J. L., Rood J. I. Virulence regions and virulence factors of the ovine footrot pathogen, Dichelobacter nodosus. FEMS Microbiol Lett. 1996 Dec 1;145(2):147–156. doi: 10.1111/j.1574-6968.1996.tb08570.x. [DOI] [PubMed] [Google Scholar]
  5. Billington S. J., Sinistaj M., Cheetham B. F., Ayres A., Moses E. K., Katz M. E., Rood J. I. Identification of a native Dichelobacter nodosus plasmid and implications for the evolution of the vap regions. Gene. 1996 Jun 12;172(1):111–116. doi: 10.1016/0378-1119(96)00032-7. [DOI] [PubMed] [Google Scholar]
  6. Bukanov N. O., Berg D. E. Ordered cosmid library and high-resolution physical-genetic map of Helicobacter pylori strain NCTC11638. Mol Microbiol. 1994 Feb;11(3):509–523. doi: 10.1111/j.1365-2958.1994.tb00332.x. [DOI] [PubMed] [Google Scholar]
  7. Censini S., Lange C., Xiang Z., Crabtree J. E., Ghiara P., Borodovsky M., Rappuoli R., Covacci A. cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14648–14653. doi: 10.1073/pnas.93.25.14648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cheetham B. F., Katz M. E. A role for bacteriophages in the evolution and transfer of bacterial virulence determinants. Mol Microbiol. 1995 Oct;18(2):201–208. doi: 10.1111/j.1365-2958.1995.mmi_18020201.x. [DOI] [PubMed] [Google Scholar]
  9. Chenault S. S., Earhart C. F. Organization of genes encoding membrane proteins of the Escherichia coli ferrienterobactin permease. Mol Microbiol. 1991 Jun;5(6):1405–1413. doi: 10.1111/j.1365-2958.1991.tb00787.x. [DOI] [PubMed] [Google Scholar]
  10. Cover T. L., Blaser M. J. Helicobacter pylori infection, a paradigm for chronic mucosal inflammation: pathogenesis and implications for eradication and prevention. Adv Intern Med. 1996;41:85–117. [PubMed] [Google Scholar]
  11. Cover T. L., Cao P., Lind C. D., Tham K. T., Blaser M. J. Correlation between vacuolating cytotoxin production by Helicobacter pylori isolates in vitro and in vivo. Infect Immun. 1993 Dec;61(12):5008–5012. doi: 10.1128/iai.61.12.5008-5012.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cover T. L., Glupczynski Y., Lage A. P., Burette A., Tummuru M. K., Perez-Perez G. I., Blaser M. J. Serologic detection of infection with cagA+ Helicobacter pylori strains. J Clin Microbiol. 1995 Jun;33(6):1496–1500. doi: 10.1128/jcm.33.6.1496-1500.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Cover T. L. The vacuolating cytotoxin of Helicobacter pylori. Mol Microbiol. 1996 Apr;20(2):241–246. doi: 10.1111/j.1365-2958.1996.tb02612.x. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Fleischmann R. D., Adams M. D., White O., Clayton R. A., Kirkness E. F., Kerlavage A. R., Bult C. J., Tomb J. F., Dougherty B. A., Merrick J. M. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science. 1995 Jul 28;269(5223):496–512. doi: 10.1126/science.7542800. [DOI] [PubMed] [Google Scholar]
  16. Foxall P. A., Hu L. T., Mobley H. L. Use of polymerase chain reaction-amplified Helicobacter pylori urease structural genes for differentiation of isolates. J Clin Microbiol. 1992 Mar;30(3):739–741. doi: 10.1128/jcm.30.3.739-741.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fujimoto S., Marshall B., Blaser M. J. PCR-based restriction fragment length polymorphism typing of Helicobacter pylori. J Clin Microbiol. 1994 Feb;32(2):331–334. doi: 10.1128/jcm.32.2.331-334.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Galli D. M., LeBlanc D. J. Characterization of pVT736-1, a rolling-circle plasmid from the gram-negative bacterium Actinobacillus actinomycetemcomitans. Plasmid. 1994 Mar;31(2):148–157. doi: 10.1006/plas.1994.1016. [DOI] [PubMed] [Google Scholar]
  19. Garner J. A., Cover T. L. Analysis of genetic diversity in cytotoxin-producing and non-cytotoxin-producing Helicobacter pylori strains. J Infect Dis. 1995 Jul;172(1):290–293. doi: 10.1093/infdis/172.1.290. [DOI] [PubMed] [Google Scholar]
  20. Go M. F., Kapur V., Graham D. Y., Musser J. M. Population genetic analysis of Helicobacter pylori by multilocus enzyme electrophoresis: extensive allelic diversity and recombinational population structure. J Bacteriol. 1996 Jul;178(13):3934–3938. doi: 10.1128/jb.178.13.3934-3938.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Jiang Q., Hiratsuka K., Taylor D. E. Variability of gene order in different Helicobacter pylori strains contributes to genome diversity. Mol Microbiol. 1996 May;20(4):833–842. doi: 10.1111/j.1365-2958.1996.tb02521.x. [DOI] [PubMed] [Google Scholar]
  22. Katz M. E., Strugnell R. A., Rood J. I. Molecular characterization of a genomic region associated with virulence in Dichelobacter nodosus. Infect Immun. 1992 Nov;60(11):4586–4592. doi: 10.1128/iai.60.11.4586-4592.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Katz M. E., Wright C. L., Gartside T. S., Cheetham B. F., Doidge C. V., Moses E. K., Rood J. I. Genetic organization of the duplicated vap region of the Dichelobacter nodosus genome. J Bacteriol. 1994 May;176(9):2663–2669. doi: 10.1128/jb.176.9.2663-2669.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Korch C., Hagblom P., Ohman H., Göransson M., Normark S. Cryptic plasmid of Neisseria gonorrhoeae: complete nucleotide sequence and genetic organization. J Bacteriol. 1985 Aug;163(2):430–438. doi: 10.1128/jb.163.2.430-438.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Logan R. P., Berg D. E. Genetic diversity of Helicobacter pylori. Lancet. 1996 Nov 30;348(9040):1462–1463. doi: 10.1016/s0140-6736(05)65885-0. [DOI] [PubMed] [Google Scholar]
  26. MacDougall J., Margarita D., Saint Girons I. Homology of a plasmid from the spirochete Treponema denticola with the single-stranded DNA plasmids. J Bacteriol. 1992 Apr;174(8):2724–2728. doi: 10.1128/jb.174.8.2724-2728.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Marchetti M., Aricò B., Burroni D., Figura N., Rappuoli R., Ghiara P. Development of a mouse model of Helicobacter pylori infection that mimics human disease. Science. 1995 Mar 17;267(5204):1655–1658. doi: 10.1126/science.7886456. [DOI] [PubMed] [Google Scholar]
  28. Nedenskov-Sørensen P., Bukholm G., Bøvre K. Natural competence for genetic transformation in Campylobacter pylori. J Infect Dis. 1990 Feb;161(2):365–366. doi: 10.1093/infdis/161.2.365. [DOI] [PubMed] [Google Scholar]
  29. Nomura A., Stemmermann G. N., Chyou P. H., Kato I., Perez-Perez G. I., Blaser M. J. Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med. 1991 Oct 17;325(16):1132–1136. doi: 10.1056/NEJM199110173251604. [DOI] [PubMed] [Google Scholar]
  31. Peterson W. L. Helicobacter pylori and peptic ulcer disease. N Engl J Med. 1991 Apr 11;324(15):1043–1048. doi: 10.1056/NEJM199104113241507. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Prewett E. J., Bickley J., Owen R. J., Pounder R. E. DNA patterns of Helicobacter pylori isolated from gastric antrum, body, and duodenum. Gastroenterology. 1992 Mar;102(3):829–833. doi: 10.1016/0016-5085(92)90165-u. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Shea C. M., McIntosh M. A. Nucleotide sequence and genetic organization of the ferric enterobactin transport system: homology to other periplasmic binding protein-dependent systems in Escherichia coli. Mol Microbiol. 1991 Jun;5(6):1415–1428. doi: 10.1111/j.1365-2958.1991.tb00788.x. [DOI] [PubMed] [Google Scholar]
  36. Smith J. M., Dowson C. G., Spratt B. G. Localized sex in bacteria. Nature. 1991 Jan 3;349(6304):29–31. doi: 10.1038/349029a0. [DOI] [PubMed] [Google Scholar]
  37. Smith J. M., Smith N. H., O'Rourke M., Spratt B. G. How clonal are bacteria? Proc Natl Acad Sci U S A. 1993 May 15;90(10):4384–4388. doi: 10.1073/pnas.90.10.4384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Staudenmaier H., Van Hove B., Yaraghi Z., Braun V. Nucleotide sequences of the fecBCDE genes and locations of the proteins suggest a periplasmic-binding-protein-dependent transport mechanism for iron(III) dicitrate in Escherichia coli. J Bacteriol. 1989 May;171(5):2626–2633. doi: 10.1128/jb.171.5.2626-2633.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Stojiljkovic I., Hantke K. Hemin uptake system of Yersinia enterocolitica: similarities with other TonB-dependent systems in gram-negative bacteria. EMBO J. 1992 Dec;11(12):4359–4367. doi: 10.1002/j.1460-2075.1992.tb05535.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Stojiljkovic I., Hantke K. Transport of haemin across the cytoplasmic membrane through a haemin-specific periplasmic binding-protein-dependent transport system in Yersinia enterocolitica. Mol Microbiol. 1994 Aug;13(4):719–732. doi: 10.1111/j.1365-2958.1994.tb00465.x. [DOI] [PubMed] [Google Scholar]
  41. Taylor D. E., Eaton M., Chang N., Salama S. M. Construction of a Helicobacter pylori genome map and demonstration of diversity at the genome level. J Bacteriol. 1992 Nov;174(21):6800–6806. doi: 10.1128/jb.174.21.6800-6806.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Taylor N. S., Fox J. G., Akopyants N. S., Berg D. E., Thompson N., Shames B., Yan L., Fontham E., Janney F., Hunter F. M. Long-term colonization with single and multiple strains of Helicobacter pylori assessed by DNA fingerprinting. J Clin Microbiol. 1995 Apr;33(4):918–923. doi: 10.1128/jcm.33.4.918-923.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. 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]
  44. Wang Y., Roos K. P., Taylor D. E. Transformation of Helicobacter pylori by chromosomal metronidazole resistance and by a plasmid with a selectable chloramphenicol resistance marker. J Gen Microbiol. 1993 Oct;139(10):2485–2493. doi: 10.1099/00221287-139-10-2485. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Bacteriology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES