Home LiteratureArticle Details
PMID: 11121067 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A whole-genome microarray reveals genetic diversity among Helicobacter pylori strains.

Salama N, Guillemin K, McDaniel TK, Sherlock G, Tompkins L, Falkow S

Abstract

Helicobacter pylori colonizes the stomach of half of the world's population, causing a wide spectrum of disease ranging from asymptomatic gastritis to ulcers to gastric cancer. Although the basis for these diverse clinical outcomes is not understood, more severe disease is associated with strains harboring a pathogenicity island. To characterize the genetic diversity of more and less virulent strains, we examined the genomic content of 15 H. pylori clinical isolates by using a whole genome H. pylori DNA microarray. We found that a full 22% of H. pylori genes are dispensable in one or more strains, thus defining a minimal functional core of 1281 H. pylori genes. While the core genes encode most metabolic and cellular processes, the strain-specific genes include genes unique to H. pylori, restriction modification genes, transposases, and genes encoding cell surface proteins, which may aid the bacteria under specific circumstances during their long-term infection of genetically diverse hosts. We observed distinct patterns of the strain-specific gene distribution along the chromosome, which may result from different mechanisms of gene acquisition and loss. Among the strain-specific genes, we have found a class of candidate virulence genes identified by their coinheritance with the pathogenicity island.

MeSH Terms
DNA, Bacterial/analysis Genes, Bacterial Genetic Variation Genome, Bacterial Helicobacter pylori/genetics,pathogenicity Humans Oligonucleotide Array Sequence Analysis/methods
Chemicals
DNA, Bacterial
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Salama N
Departments of Microbiology and Immunology, and Genetics, Stanford University School of Medicine, Stanford, CA 94305-5124, USA. [email protected]
Guillemin K
McDaniel T K
Sherlock G
Tompkins L
Falkow S
References (34)
34 references, click to expand
  1. Altered states: involvement of phosphorylated CagA in the induction of host cellular growth changes by Helicobacter pylori.
    Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14559-64 PMID: 10588744
  2. Clinical relevance of the Helicobacter pylori gene for blood-group antigen-binding adhesin.
    Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12778-83 PMID: 10535999
  3. Tyrosine phosphorylation of the Helicobacter pylori CagA antigen after cag-driven host cell translocation.
    Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1263-8 PMID: 10655519
  4. Analysis of the genetic diversity of Helicobacter pylori: the tale of two genomes.
    J Mol Med (Berl). 1999 Dec;77(12):834-46 PMID: 10682319
  5. Helicobacter pylori CagA protein can be tyrosine phosphorylated in gastric epithelial cells.
    J Exp Med. 2000 Feb 21;191(4):593-602 PMID: 10684851
  6. Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion.
    Science. 2000 Feb 25;287(5457):1497-500 PMID: 10688800
  7. Lateral gene transfer and the nature of bacterial innovation.
    Nature. 2000 May 18;405(6784):299-304 PMID: 10830951
  8. Identification of type II restriction and modification systems in Helicobacter pylori reveals their substantial diversity among strains.
    Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9671-6 PMID: 10944229
  9. Characterization of Helicobacter pylori urease mutants.
    Infect Immun. 1992 May;60(5):1883-9 PMID: 1563778
  10. 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):5791-5 PMID: 8516329
  11. Expression of interleukin 8 and CD54 by human gastric epithelium after Helicobacter pylori infection in vitro.
    Gastroenterology. 1995 Jan;108(1):65-74 PMID: 7806065
  12. 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.
    Infect Immun. 1995 Jan;63(1):94-8 PMID: 7806390
  13. Development of a mouse model of Helicobacter pylori infection that mimics human disease.
    Science. 1995 Mar 17;267(5204):1655-8 PMID: 7886456
  14. Helicobacter pylori induced interleukin-8 expression in gastric epithelial cells is associated with CagA positive phenotype.
    J Clin Pathol. 1995 Jan;48(1):41-5 PMID: 7706517
  15. 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):14648-53 PMID: 8962108
  16. A standardized mouse model of Helicobacter pylori infection: introducing the Sydney strain.
    Gastroenterology. 1997 Apr;112(4):1386-97 PMID: 9098027
  17. The complete genome sequence of the gastric pathogen Helicobacter pylori.
    Nature. 1997 Aug 7;388(6642):539-47 PMID: 9252185
  18. Corrected identity of isolates of Helicobacter pylori reference strain NCTC11637.
    Helicobacter. 1997 Mar;2(1):48-52 PMID: 9432323
  19. Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging.
    Science. 1998 Jan 16;279(5349):373-7 PMID: 9430586
  20. Epithelial attachment alters the outcome of Helicobacter pylori infection.
    Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3925-30 PMID: 9520469
  21. Proteins encoded by the cag pathogenicity island of Helicobacter pylori are required for NF-kappaB activation.
    Infect Immun. 1998 May;66(5):2346-8 PMID: 9573128
  22. Analyses of the cag pathogenicity island of Helicobacter pylori.
    Mol Microbiol. 1998 Apr;28(1):37-53 PMID: 9593295
  23. cagA positive and negative Helicobacter pylori strains are simultaneously present in the stomach of most patients with non-ulcer dyspepsia: relevance to histological damage.
    Gut. 1998 Jun;42(6):772-8 PMID: 9691913
  24. Selfishness and death: raison d'être of restriction, recombination and mitochondria.
    Trends Genet. 1998 Sep;14(9):368-74 PMID: 9769733
  25. PCR-based subtractive hybridization and differences in gene content among strains of Helicobacter pylori.
    Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13108-13 PMID: 9789049
  26. Helicobacter pylori--a conundrum of genetic diversity.
    Microbiology. 1998 Nov;144 ( Pt 11):2925-39 PMID: 9846728
  27. Cluster analysis and display of genome-wide expression patterns.
    Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8 PMID: 9843981
  28. Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori.
    Nature. 1999 Jan 14;397(6715):176-80 PMID: 9923682
  29. Assigning protein functions by comparative genome analysis: protein phylogenetic profiles.
    Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4285-8 PMID: 10200254
  30. Helicobacter pylori virulence and genetic geography.
    Science. 1999 May 21;284(5418):1328-33 PMID: 10334982
  31. DNA arrays for analysis of gene expression.
    Methods Enzymol. 1999;303:179-205 PMID: 10349646
  32. Metabolism and genetics of Helicobacter pylori: the genome era.
    Microbiol Mol Biol Rev. 1999 Sep;63(3):642-74 PMID: 10477311
  33. Helicobacter pylori physiology predicted from genomic comparison of two strains.
    Microbiol Mol Biol Rev. 1999 Sep;63(3):675-707 PMID: 10477312
  34. Quasispecies development of Helicobacter pylori observed in paired isolates obtained years apart from the same host.
    J Infect Dis. 2000 Jan;181(1):273-82 PMID: 10608776
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
2000-12-19
Pages
14668-73
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC18976
Subset
IM
Grants
NIAID NIH HHS · R01 AI038459 · United States
NIAID NIH HHS · AI38459 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]