Home LiteratureArticle Details
PMID: 12761138 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

pH-regulated gene expression of the gastric pathogen Helicobacter pylori.

Infection and immunity ·Vol. 71 ·No. 6 ·2003-06-00 ·Pages 3529-39

Merrell DS, Goodrich ML, Otto G, Tompkins LS, Falkow S

Abstract

Colonization by the gastric pathogen Helicobacter pylori has been shown to be intricately linked to the development of gastritis, ulcers, and gastric malignancy. Little is known about mechanisms employed by the bacterium that help it adapt to the hostile environment of the human stomach. In an effort to extend our knowledge of these mechanisms, we utilized spotted-DNA microarrays to characterize the response of H. pylori to low pH. Expression of approximately 7% of the bacterial genome was reproducibly altered by shift to low pH. Analysis of the differentially expressed genes led to the discovery that acid exposure leads to profound changes in motility of H. pylori, as a larger percentage of acid-exposed bacterial cells displayed motility and moved at significantly higher speeds. In contrast to previous publications, we found that expression of the bacterial virulence gene cagA was strongly repressed by acid exposure. Furthermore, this transcriptional repression was reflected at the level of protein accumulation in the H. pylori cell.

MeSH Terms
Ammonia/metabolism Animals Antigens, Bacterial/genetics Bacterial Outer Membrane Proteins/genetics Bacterial Proteins/genetics Flagellin/biosynthesis Gene Expression Regulation, Bacterial Gerbillinae Helicobacter pylori/genetics,physiology Humans Hydrogen-Ion Concentration Male Oligonucleotide Array Sequence Analysis Up-Regulation
Chemicals
Antigens, Bacterial Bacterial Outer Membrane Proteins Bacterial Proteins cagA protein, Helicobacter pylori Flagellin flaA protein, bacteria flaB flagellin Ammonia
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Merrell D Scott
Department of Microbiology and Immunology, Stanford School of Medicine, California 94305, USA. dmerrell@stanford.edu
Goodrich Maria L
Otto Glen
Tompkins Lucy S
Falkow Stanley
References (79)
79 references, click to expand
  1. Aflagellated mutants of Helicobacter pylori generated by genetic transformation of naturally competent strains using transposon shuttle mutagenesis.
    Mol Microbiol. 1993 May;8(4):753-60 PMID: 8332066
  2. A urease-negative mutant of Helicobacter pylori constructed by allelic exchange mutagenesis lacks the ability to colonize the nude mouse stomach.
    Infect Immun. 1994 Aug;62(8):3586-9 PMID: 8039935
  3. Effect of gastric pH on urease-dependent colonization of gnotobiotic piglets by Helicobacter pylori.
    Infect Immun. 1994 Sep;62(9):3604-7 PMID: 8063376
  4. Isolation and characterization of a conserved porin protein from Helicobacter pylori.
    J Bacteriol. 1995 Oct;177(19):5447-52 PMID: 7559328
  5. Molecular biology of microbial ureases.
    Microbiol Rev. 1995 Sep;59(3):451-80 PMID: 7565414
  6. Aminoacid utilization by Helicobacter pylori.
    Int J Biochem Cell Biol. 1995 Oct;27(10):1085-93 PMID: 7496998
  7. Adherence to gastric epithelial cells induces expression of a Helicobacter pylori gene, iceA, that is associated with clinical outcome.
    Proc Assoc Am Physicians. 1998 Nov-Dec;110(6):531-44 PMID: 9824536
  8. Crystal structure of the outer membrane active transporter FepA from Escherichia coli.
    Nat Struct Biol. 1999 Jan;6(1):56-63 PMID: 9886293
  9. Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori.
    Nature. 1999 Jan 14;397(6715):176-80 PMID: 9923682
  10. Helicobacter pylori-induced chronic active gastritis, intestinal metaplasia, and gastric ulcer in Mongolian gerbils.
    Am J Pathol. 1999 Mar;154(3):951-60 PMID: 10079274
  11. Genetic and functional characterization of the alpAB gene locus essential for the adhesion of Helicobacter pylori to human gastric tissue.
    Mol Microbiol. 1999 Mar;31(5):1537-48 PMID: 10200971
  12. Functional analysis of the roles of FliQ and FlhB in flagellar expression in Helicobacter pylori.
    FEMS Microbiol Lett. 1999 May 1;174(1):33-9 PMID: 10234819
  13. Helicobacter pylori virulence and genetic geography.
    Science. 1999 May 21;284(5418):1328-33 PMID: 10334982
  14. Cloning, sequence analysis, and expression of ansB from Pseudomonas fluorescens, encoding periplasmic glutaminase/asparaginase.
    FEMS Microbiol Lett. 1999 Sep 15;178(2):327-35 PMID: 10499283
  15. Urease plays an important role in the chemotactic motility of Helicobacter pylori in a viscous environment.
    Infect Immun. 1998 Oct;66(10):4832-7 PMID: 9746586
  16. 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
  17. Surface localization of Helicobacter pylori urease and a heat shock protein homolog requires bacterial autolysis.
    Infect Immun. 1996 Mar;64(3):905-12 PMID: 8641799
  18. Colonization of gnotobiotic piglets by Helicobacter pylori deficient in two flagellin genes.
    Infect Immun. 1996 Jul;64(7):2445-8 PMID: 8698465
  19. The effect of environmental pH on the proton motive force of Helicobacter pylori.
    Gastroenterology. 1996 Oct;111(4):886-900 PMID: 8831583
  20. Effect of growth phase and acid shock on Helicobacter pylori cagA expression.
    Infect Immun. 1996 Nov;64(11):4501-7 PMID: 8890198
  21. 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
  22. Analysis of F1F0-ATPase from Helicobacter pylori.
    Infect Immun. 1997 Jul;65(7):2640-7 PMID: 9199431
  23. The complete genome sequence of the gastric pathogen Helicobacter pylori.
    Nature. 1997 Aug 7;388(6642):539-47 PMID: 9252185
  24. Helicobacter pylori.
    Clin Microbiol Rev. 1997 Oct;10(4):720-41 PMID: 9336670
  25. Identification and characterization of an aliphatic amidase in Helicobacter pylori.
    Mol Microbiol. 1997 Sep;25(5):989-98 PMID: 9364923
  26. The role of internal urease in acid resistance of Helicobacter pylori.
    Gastroenterology. 1998 Jan;114(1):58-70 PMID: 9428219
  27. Epidemiology of Helicobacter pylori infection with special reference to professional risk.
    J Physiol Pharmacol. 1997 Sep;48 Suppl 4:3-17 PMID: 9440051
  28. Helicobacter pylori and gastric diseases.
    BMJ. 1998 May 16;316(7143):1507-10 PMID: 9582144
  29. Analyses of the cag pathogenicity island of Helicobacter pylori.
    Mol Microbiol. 1998 Apr;28(1):37-53 PMID: 9593295
  30. Molecular characterization of two-component systems of Helicobacter pylori.
    J Bacteriol. 2000 Apr;182(8):2068-76 PMID: 10735847
  31. Acid-induced expression of an LPS-associated gene in Helicobacter pylori.
    Mol Microbiol. 1998 Oct;30(1):19-31 PMID: 9786182
  32. Isolation and characterization of a family of porin proteins from Helicobacter pylori.
    Infect Immun. 1995 Apr;63(4):1567-72 PMID: 7534278
  33. Isolation of the Helicobacter pylori recA gene and involvement of the recA region in resistance to low pH.
    Infect Immun. 1995 Jun;63(6):2185-93 PMID: 7768597
  34. Comparative ultrastructural and functional studies of Helicobacter pylori and Helicobacter mustelae flagellin mutants: both flagellin subunits, FlaA and FlaB, are necessary for full motility in Helicobacter species.
    J Bacteriol. 1995 Jun;177(11):3010-20 PMID: 7768796
  35. The complex flagella of gastric Helicobacter species.
    Trends Microbiol. 1995 May;3(5):168-70; discussion 170-1 PMID: 7627454
  36. Inability of an isogenic urease-negative mutant stain of Helicobacter mustelae to colonize the ferret stomach.
    Infect Immun. 1995 Sep;63(9):3722-5 PMID: 7642314
  37. Molecular cloning and characterization of the Helicobacter pylori fliD gene, an essential factor in flagellar structure and motility.
    J Bacteriol. 1999 Nov;181(22):6969-76 PMID: 10559162
  38. Helicobacter pylori rocF is required for arginase activity and acid protection in vitro but is not essential for colonization of mice or for urease activity.
    J Bacteriol. 1999 Dec;181(23):7314-22 PMID: 10572136
  39. Recombinational repair of DNA damage in Escherichia coli and bacteriophage lambda.
    Microbiol Mol Biol Rev. 1999 Dec;63(4):751-813, table of contents PMID: 10585965
  40. 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
  41. A H+-gated urea channel: the link between Helicobacter pylori urease and gastric colonization.
    Science. 2000 Jan 21;287(5452):482-5 PMID: 10642549
  42. Identification of the urease operon in Helicobacter pylori and its control by mRNA decay in response to pH.
    Mol Microbiol. 2000 Jun;36(5):1071-84 PMID: 10844692
  43. Evidence for a signaling system in Helicobacter pylori: detection of a luxS-encoded autoinducer.
    J Bacteriol. 2000 Jul;182(13):3638-43 PMID: 10850976
  44. Comparative genomics of Helicobacter pylori: analysis of the outer membrane protein families.
    Infect Immun. 2000 Jul;68(7):4155-68 PMID: 10858232
  45. Adherence of isogenic flagellum-negative mutants of Helicobacter pylori and Helicobacter mustelae to human and ferret gastric epithelial cells.
    Infect Immun. 2000 Jul;68(7):4335-9 PMID: 10858255
  46. Identification of loci essential for the growth of Helicobacter pylori under acidic conditions.
    J Infect Dis. 2000 Nov;182(5):1566-9 PMID: 11023484
  47. A whole-genome microarray reveals genetic diversity among Helicobacter pylori strains.
    Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14668-73 PMID: 11121067
  48. The Stanford Microarray Database.
    Nucleic Acids Res. 2001 Jan 1;29(1):152-5 PMID: 11125075
  49. Vacuolating cytotoxin of Helicobacter pylori plays a role during colonization in a mouse model of infection.
    Infect Immun. 2001 Feb;69(2):730-6 PMID: 11159961
  50. Acid-induced gene expression in Helicobacter pylori: study in genomic scale by microarray.
    Infect Immun. 2001 Mar;69(3):1679-86 PMID: 11179343
  51. The ToxR-mediated organic acid tolerance response of Vibrio cholerae requires OmpU.
    J Bacteriol. 2001 May;183(9):2746-54 PMID: 11292792
  52. New approaches for validation of lethal phenotypes and genetic reversion in Helicobacter pylori.
    Helicobacter. 2001 Mar;6(1):15-23 PMID: 11328361
  53. Identification of the Helicobacter pylori anti-sigma28 factor.
    Mol Microbiol. 2001 Jul;41(2):477-87 PMID: 11489132
  54. Characterization of the low-pH responses of Helicobacter pylori using genomic DNA arrays.
    Microbiology. 2001 Aug;147(Pt 8):2285-92 PMID: 11496005
  55. Phase variation in the Helicobacter pylori phospholipase A gene and its role in acid adaptation.
    Infect Immun. 2001 Dec;69(12):7334-40 PMID: 11705905
  56. Identification of target genes regulated by the two-component system HP166-HP165 of Helicobacter pylori.
    J Bacteriol. 2002 Jan;184(2):350-62 PMID: 11751811
  57. The Helicobacter pylori homologue of the ferric uptake regulator is involved in acid resistance.
    Infect Immun. 2002 Feb;70(2):606-11 PMID: 11796589
  58. SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein.
    Science. 2002 Jan 25;295(5555):683-6 PMID: 11743164
  59. Src is the kinase of the Helicobacter pylori CagA protein in vitro and in vivo.
    J Biol Chem. 2002 Mar 1;277(9):6775-8 PMID: 11788577
  60. Helicobacter pylori uses motility for initial colonization and to attain robust infection.
    Infect Immun. 2002 Apr;70(4):1984-90 PMID: 11895962
  61. c-Src/Lyn kinases activate Helicobacter pylori CagA through tyrosine phosphorylation of the EPIYA motifs.
    Mol Microbiol. 2002 Feb;43(4):971-80 PMID: 11929545
  62. Identification of novel factors involved in colonization and acid tolerance of Vibrio cholerae.
    Mol Microbiol. 2002 Mar;43(6):1471-91 PMID: 11952899
  63. Host-induced epidemic spread of the cholera bacterium.
    Nature. 2002 Jun 6;417(6889):642-5 PMID: 12050664
  64. Transcriptional response of Saccharomyces cerevisiae to DNA-damaging agents does not identify the genes that protect against these agents.
    Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8778-83 PMID: 12077312
  65. Determination of the transcriptome of Vibrio cholerae during intraintestinal growth and midexponential phase in vitro.
    Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1286-91 PMID: 12552086
  66. Gene expression profiling of Helicobacter pylori reveals a growth-phase-dependent switch in virulence gene expression.
    Infect Immun. 2003 May;71(5):2643-55 PMID: 12704139
  67. Maltose transport in Escherichia coli K12. A comparison of transport kinetics in wild-type and lambda-resistant mutants as measured by fluorescence quenching.
    Eur J Biochem. 1976 May 17;65(1):13-9 PMID: 776623
  68. Structure of the metJBLF cluster in Escherichia coli K12. Sequence of the metB structural gene and of the 5'- and 3'-flanking regions of the metBL operon.
    J Biol Chem. 1983 Dec 25;258(24):14868-71 PMID: 6361020
  69. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration.
    Lancet. 1984 Jun 16;1(8390):1311-5 PMID: 6145023
  70. Pore-forming activity of the Tsx protein from the outer membrane of Escherichia coli. Demonstration of a nucleoside-specific binding site.
    J Biol Chem. 1988 Feb 15;263(5):2493-9 PMID: 3276691
  71. Epidemiology and pathophysiology of Campylobacter pylori infections.
    Rev Infect Dis. 1990 Jan-Feb;12 Suppl 1:S99-106 PMID: 2406864
  72. Identification, characterization, and spatial localization of two flagellin species in Helicobacter pylori flagella.
    J Bacteriol. 1991 Feb;173(3):937-46 PMID: 1704004
  73. Shuttle cloning and nucleotide sequences of Helicobacter pylori genes responsible for urease activity.
    J Bacteriol. 1991 Mar;173(6):1920-31 PMID: 2001995
  74. Helicobacter pylori infection and the risk of gastric carcinoma.
    N Engl J Med. 1991 Oct 17;325(16):1127-31 PMID: 1891020
  75. Expression of Helicobacter pylori urease genes in Escherichia coli grown under nitrogen-limiting conditions.
    J Bacteriol. 1992 Apr;174(8):2466-73 PMID: 1313413
  76. Construction of isogenic urease-negative mutants of Helicobacter pylori by allelic exchange.
    J Bacteriol. 1992 Jul;174(13):4212-7 PMID: 1320607
  77. Cloning and genetic characterization of a Helicobacter pylori flagellin gene.
    Mol Microbiol. 1992 Oct;6(19):2863-74 PMID: 1435261
  78. 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):3278-88 PMID: 8501031
  79. 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
Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/IAI.71.6.3529-3539.2003
Email
dmerrell@stanford.edu
Published
2003-06-00
Pages
3529-39
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC155744
Subset
IM
Grants
NIAID NIH HHS · T32 AI007502 · United States
NIAID NIH HHS · AI07502-06 · United States
NCI NIH HHS · R01 CA092229 · United States
NIAID NIH HHS · AI38459 · United States
NCI NIH HHS · CA92229 · United States
NIDDK NIH HHS · DK56339 · United States
NIDDK NIH HHS · P30 DK056339 · United States
NIAID NIH HHS · R01 AI038459 · United States
External Links
PubMed source DOI: 10.1128/IAI.71.6.3529-3539.2003 PMC Full Text View journal details
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: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2