1887

Abstract

Phase variation is a common mechanism used by pathogenic bacteria to generate intra-strain diversity that is important in niche adaptation and is strongly associated with virulence determinants. Previous analyses of the complete sequences of the strains 26695 and J99 have identified 36 putative phase-variable genes among the two genomes through their association with homopolymeric tracts and dinucleotide repeats. Here a comparative analysis of the two genomes is reported and an updated and expanded list of 46 candidate phase-variable genes in is described. These have been systematically investigated by PCR and sequencing for the presence of the genes, and the presence and variability in length of the repeats in strains 26695 and J99 and in a collection of unrelated strains representative of the main global subdivisions recently suggested. This provides supportive evidence for the phase variability of 30 of the 46 candidates. Other differences in this subset of genes were observed (i) in the repeats, which can be present or absent among the strains, or stabilized in different strains and (ii) in the gene-complements of the strains. Differences between genes were not consistently correlated with the geographic population distribution of the strains. This study extends and provides new evidence for variation of this type in , and of the high degree of diversity of the repertoire of genes which display phase-variable switching within individual strains.

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2004-04-01
2020-04-06
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References

  1. Achtman M., Azuma T., Berg D. E..7 other authors 1999; Recombination and clonal groupings within Helicobacter pylori from different geographical regions. Mol Microbiol32:459–470[CrossRef]
    [Google Scholar]
  2. Akopyants N. S., Clifton S. W., Kersulyte D..7 other authors 1998; Analyses of the cag pathogenicity island of Helicobacter pylori. Mol Microbiol28:37–53
    [Google Scholar]
  3. Alm R. A., Ling L. S., Moir D. T..20 other authors 1999; Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature397:176–180[CrossRef]
    [Google Scholar]
  4. Appelmelk B. J., Shiberu B., Trinks C..10 other authors 1998; Phase variation in Helicobacter pylori lipopolysaccharide. Infect Immun66:70–76
    [Google Scholar]
  5. Appelmelk B. J., Martin S. L., Monteiro M. A..10 other authors 1999; Phase variation in Helicobacter pylori lipopolysaccharide due to changes in the lengths of poly(C) tracts in alpha3-fucosyltransferase genes. Infect Immun67:5361–5366
    [Google Scholar]
  6. Appelmelk B. J., Martino M. C., Veenhof E..7 other authors 2000; Phase variation in H type I and Lewis a epitopes of Helicobacter pylori lipopolysaccharide. Infect Immun68:5928–5932[CrossRef]
    [Google Scholar]
  7. Atherton J. C., Peek R. M. Jr, Tham K. T., Cover T. L., Blaser M. J.. 1997; Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori. Gastroenterology112:92–99[CrossRef]
    [Google Scholar]
  8. Björkholm B. M., Guruge J. L., Oh J. D..8 other authors 2002; Colonization of germ-free transgenic mice with genotyped Helicobacter pylori strains from a case-control study of gastric cancer reveals a correlation between host responses and HsdS components of type I restriction-modification systems. J Biol Chem277:34191–34197[CrossRef]
    [Google Scholar]
  9. Blaser M. J.. 1997; Ecology of Helicobacter pylori in the human stomach. J Clin Invest100:759–762[CrossRef]
    [Google Scholar]
  10. Boneca I. G., de Reuse H., Epinat J. C., Pupin M., Labigne A., Moszer I.. 2003; A revised annotation and comparative analysis of Helicobacter pylori genomes. Nucleic Acids Res31:1704–1714[CrossRef]
    [Google Scholar]
  11. Bonfield J. K., Beal K. F., Betts M. J., Staden R.. 2002; Trev: a DNA trace editor and viewer. Bioinformatics18:194–195[CrossRef]
    [Google Scholar]
  12. Bunn J. E., MacKay W. G., Thomas J. E., Reid D. C., Weaver L. T.. 2002; Detection of Helicobacter pylori DNA in drinking water biofilms: implications for transmission in early life. Lett Appl Microbiol34:450–454[CrossRef]
    [Google Scholar]
  13. De Bolle X., Bayliss C. D., Saunders N. J., Hood D. W., Moxon E. R., Field D., van de Ven T.. 2000; The length of a tetranucleotide repeat tract in Haemophilus influenzae determines the phase variation rate of a gene with homology to type III DNA methyltransferases. Mol Microbiol35:211–222[CrossRef]
    [Google Scholar]
  14. de Vries N., Duinsbergen D., Kuipers E. J., Pot R. G., Wiesenekker P., Penn C. W., Van Vliet A. H., Vandenbroucke-Grauls C. M., Kusters J. G.. 2002; Transcriptional phase variation of a type III restriction-modification system in Helicobacter pylori. J Bacteriol184:6615–6623[CrossRef]
    [Google Scholar]
  15. Durbin R., Thierry-Mieg J. T.. 1991; A C. elegans DataBase. Documentation, code and data available fromhttp://www.acedb.org
  16. Falush D., Kraft C., Taylor N. S., Correa P., Fox J. G., Achtman M., Suerbaum S.. 2001; Recombination and mutation during long-term gastric colonization by Helicobacter pylori: estimates of clock rates, recombination size, and minimal age. Proc Natl Acad Sci U S A98:15056–15061[CrossRef]
    [Google Scholar]
  17. Falush D., Wirth T., Linz B.. & 15 other authors. 2003; Traces of human migrations in Helicobacter pylori populations. Science299:1582–1585[CrossRef]
    [Google Scholar]
  18. Go M. F., Kapur V., Graham D. Y., Musser J. M.. 1996; Population genetic analysis of Helicobacter pylori by multilocus enzyme electrophoresis: extensive allelic diversity and recombinational population structure. J Bacteriol178:3934–3938
    [Google Scholar]
  19. Hammerschmidt S., Muller A., Sillmann H..7 other authors 1996; Capsule phase variation in Neisseria meningitidis serogroup B by slipped-strand mispairing in the polysialyltransferase gene (siaD): correlation with bacterial invasion and the outbreak of meningococcal disease. Mol Microbiol20:1211–1220[CrossRef]
    [Google Scholar]
  20. Hood D. W., Deadman M. E., Jennings M. P., Bisercic M., Fleischmann R. D., Venter J. C., Moxon E. R.. 1996; DNA repeats identify novel virulence genes in Haemophilus influenzae. Proc Natl Acad Sci U S A93:11121–11125[CrossRef]
    [Google Scholar]
  21. Ilver D., Arnqvist A., Ogren J..7 other authors 1998; Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging. Science279:373–377[CrossRef]
    [Google Scholar]
  22. Jennings M. P., Hood D. W., Peak I. R., Virji M., Moxon E. R.. 1995; Molecular analysis of a locus for the biosynthesis and phase-variable expression of the lacto-N-neotetraose terminal lipopolysaccharide structure in Neisseria meningitidis. Mol Microbiol18:729–740[CrossRef]
    [Google Scholar]
  23. Josenhans C., Eaton K. A., Thevenot T., Suerbaum S.. 2000; Switching of flagellar motility in Helicobacter pylori by reversible length variation of a short homopolymeric sequence repeat infliP, a gene encoding a basal body protein. Infect Immun68:4598–4603[CrossRef]
    [Google Scholar]
  24. Lee A., O'Rourke J., De Ungria M. C., Robertson B., Daskalopoulos G., Dixon M. F.. 1997; A standardized mouse model of Helicobacter pylori infection: introducing the Sydney strain. Gastroenterology112:1386–1397[CrossRef]
    [Google Scholar]
  25. Logan R. P., Berg D. E.. 1996; Genetic diversity of Helicobacter pylori. Lancet348:1462–1463[CrossRef]
    [Google Scholar]
  26. Logan S. M., Conlan J. W., Monteiro M. A., Wakarchuk W. W., Altman E.. 2000; Functional genomics of Helicobacter pylori: identification of a beta-1,4 galactosyltransferase and generation of mutants with altered lipopolysaccharide. Mol Microbiol35:1156–1167[CrossRef]
    [Google Scholar]
  27. Mahdavi J., Sonden B., Hurtig M.. & 20 other authors. 2002; Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation. Science297:573–578[CrossRef]
    [Google Scholar]
  28. Majmudar P., Shah S. M., Dhunjibhoy K. R., Desai H. G.. 1990; Isolation of Helicobacter pylori from dental plaques in healthy volunteers. Indian J Gastroenterol9:271–272
    [Google Scholar]
  29. Marshall B.. 1994; Helicobacter pylori. Am J Gastroenterol89:S116–S118
    [Google Scholar]
  30. Marshall B. J., Warren J. R.. 1984; Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet1:1311–1315
    [Google Scholar]
  31. Martin P., Van De Ven T., Mouchel N., Jeffries A. C., Hood D. W., Moxon E. R.. 2003; Experimentally revised repertoire of putative contingency loci in Neisseria meningitidis strain MC58: evidence for a novel mechanism of phase variation. Mol Microbiol50:245–257[CrossRef]
    [Google Scholar]
  32. Nomura A., Stemmermann G. N., Chyou P. H., Perez-Perez G. I., Blaser M. J.. 1994; Helicobacter pylori infection and the risk for duodenal and gastric ulceration. Ann Intern Med120:977–981[CrossRef]
    [Google Scholar]
  33. Park S. R., Mackay W. G., Reid D. C.. 2001; Helicobacter sp. recovered from drinking water biofilm sampled from a water distribution system. Water Res35:1624–1626[CrossRef]
    [Google Scholar]
  34. Parkhill J., Wren B. W., Mungall K.. & 18 other authors. 2000; The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences. Nature403:665–668[CrossRef]
    [Google Scholar]
  35. Parsonnet J.. 1995; The incidence of Helicobacter pylori infection. Aliment Pharmacol Ther9:45–51
    [Google Scholar]
  36. Parsonnet J., Hansen S., Rodriguez L., Gelb A. B., Warnke R. A., Jellum E., Orentreich N., Vogelman J. H., Friedman G. D.. 1994; Helicobacter pylori infection and gastric lymphoma. N Engl J Med330:1267–1271[CrossRef]
    [Google Scholar]
  37. Peck B., Ortkamp M., Diehl K. D., Hundt E., Knapp B.. 1999; Conservation, localization and expression of HopZ, a protein involved in adhesion of Helicobacter pylori. Nucleic Acids Res27:3325–3333[CrossRef]
    [Google Scholar]
  38. Rocha E. P., Pradillon O., Bui H., Sayada C., Denamur E.. 2002; A new family of highly variable proteins in the Chlamydophila pneumoniae genome. Nucleic Acids Res30:4351–4360[CrossRef]
    [Google Scholar]
  39. Salaün L., Audibert C., Le Lay G., Burucoa C., Fauchere J. L., Picard B.. 1998; Panmictic structure of Helicobacter pylori demonstrated by the comparative study of six genetic markers. FEMS Microbiol Lett161:231–239[CrossRef]
    [Google Scholar]
  40. Salaün L., Snyder L. A., Saunders N. J.. 2003; Adaptation by phase variation in pathogenic bacteria. Adv Appl Microbiol52:263–301
    [Google Scholar]
  41. Saunders N. J.. 1999; Bacterial phase variation associated with repetitive DNA. PhD thesis The Open University;
  42. Saunders N. J.. 2003; Evasion of antibody responses: bacterial phase variation. In Bacterial Evasion of Host Immune Responses pp.103–124 Edited by Henderson B., Oyston P. C. F.. Cambridge: Cambridge University Press;
    [Google Scholar]
  43. Saunders N. J., Peden J. F., Hood D. W., Moxon E. R.. 1998; Simple sequence repeats in the Helicobacter pylori genome. Mol Microbiol27:1091–1098[CrossRef]
    [Google Scholar]
  44. Saunders N. J., Jeffries A. C., Peden J. F., Hood D. W., Tettelin H., Rappuoli R., Moxon E. R.. 2000; Repeat-associated phase variable genes in the complete genome sequence of Neisseria meningitidis strain MC58. Mol Microbiol37:207–215[CrossRef]
    [Google Scholar]
  45. Snyder L. A., Butcher S. A., Saunders N. J.. 2001; Comparative whole-genome analyses reveal over 100 putative phase-variable genes in the pathogenic Neisseria spp. Microbiology147:2321–2332
    [Google Scholar]
  46. Suerbaum S., Smith J. M., Bapumia K., Morelli G., Smith N. H., Kunstmann E., Dyrek I., Achtman M.. 1998; Free recombination within Helicobacter pylori. Proc Natl Acad Sci U S A95:12619–12624[CrossRef]
    [Google Scholar]
  47. Tannaes T., Dekker N., Bukholm G., Bijlsma J. J., Appelmelk B. J.. 2001; Phase variation in the Helicobacter pylori phospholipase A gene and its role in acid adaptation. Infect Immun69:7334–7340[CrossRef]
    [Google Scholar]
  48. Tettelin H., Saunders N. J., Heidelberg J..39 other authors 2000; Complete genome sequence of Neisseria meningitidis serogroup B strain MC58. Science287:1809–1815[CrossRef]
    [Google Scholar]
  49. Tomb J. F., White O., Kerlavage A. R..39 other authors 1997; The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature388:539–547[CrossRef]
    [Google Scholar]
  50. van Ham S. M., van Alphen L., Mooi F. R., van Putten J. P.. 1993; Phase variation of Haemophilus influenzae fimbriae: transcriptional control of two divergent genes through a variable combined promoter region. Cell73:1187–1196[CrossRef]
    [Google Scholar]
  51. Wang G., Rasko D. A., Sherburne R., Taylor D. E.. 1999; Molecular genetic basis for the variable expression of Lewis Y antigen in Helicobacter pylori: analysis of the alpha (1,2) fucosyltransferase gene. Mol Microbiol31:1265–1274[CrossRef]
    [Google Scholar]
  52. Wassenaar T. M., Wagenaar J. A., Rigter A., Fearnley C., Newell D. G., Duim B.. 2002; Homonucleotide stretches in chromosomal DNA of Campylobacter jejuni display high frequency polymorphism as detected by direct PCR analysis. FEMS Microbiol Lett212:77–85[CrossRef]
    [Google Scholar]
  53. Yamaoka Y., Kwon D. H., Graham D. Y.. 2000; A M(r) 34,000 proinflammatory outer membrane protein (oipA) of Helicobacter pylori. Proc Natl Acad Sci U S A97:7533–7538[CrossRef]
    [Google Scholar]
  54. Yamaoka Y., Kikuchi S., el-Zimaity H. M., Gutierrez O., Osato M. S., Graham D. Y.. 2002a; Importance of Helicobacter pylori oipA in clinical presentation, gastric inflammation, and mucosal interleukin 8 production. Gastroenterology123:414–424[CrossRef]
    [Google Scholar]
  55. Yamaoka Y., Kita M., Kodama T., Imamura S., Ohno T., Sawai N., Ishimaru A., Imanishi J., Graham D. Y.. 2002b; Helicobacter pylori infection in mice: role of outer membrane proteins in colonization and inflammation. Gastroenterology123:1992–2004[CrossRef]
    [Google Scholar]
  56. Yogev D., Rosengarten R., Watson-McKown R., Wise K. S.. 1991; Molecular basis of Mycoplasma surface antigenic variation: a novel set of divergent genes undergo spontaneous mutation of periodic coding regions and 5′ regulatory sequences. EMBO J10:4069–4079
    [Google Scholar]
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