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  • 1
    Electronic Resource
    Electronic Resource
    The role of Helicobacter pylori virulence factors in interleukin production by monocytic cells (2001)
    Oxford, UK : Blackwell Publishing Ltd
    FEMS microbiology letters 196 (2001), S. 0 
    Details
    ISSN: 1574-6968
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Helicobacter pylori infection results in chronic gastritis, which is initiated by the release of cytokines like interleukin (IL)-12 and IL-8 from mononuclear cells, and IL-8 from gastric epithelial cells. The severity of gastritis is influenced both by host factors and by bacterial factors such as the Cag proteins and the vacuolating cytotoxin VacA. Amounts of IL-12 and IL-8 produced by monocytic THP-1 cells differed considerably between the eight H. pylori isolates tested, but in contrast to H. pylori-induced IL-8 production by gastric epithelial cells, did not correlate to the Cag and VacA types of the strains. Apparently, in addition to Cag and VacA, other bacterial factors determine the extent in which H. pylori induced IL production in monocytes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1574-6968.2001.tb10570.x
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  • 2
    Electronic Resource
    Electronic Resource
    Helicobacter pylori and Nonmalignant Diseases (2004)
    Oxford, UK : Blackwell Science Ltd
    Helicobacter 9 (2004), S. 0 
    Details
    ISSN: 1523-5378
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: This paper reviews the new literature from the past year on the association between colonization with Helicobacter pylori and non-malignant disease of the upper gastrointestinal tract. This issue has, in the past year, remained a topic of wide research interest yielding many important new data. These data show that H. pylori eradication is the most effective therapy for peptic ulcer disease, but that a considerable proportion of ulcer patients remain to have dyspeptic symptoms. The discussion on the interaction between H. pylori and NSAID use in the etiology of ulcer disease has not yet been settled. Several studies, both from Asia and Europe, now reported that H. pylori eradication has a minimal effect on the primary prevention of ulcer disease in NSAID users, but eradication appears of relevance for the secondary prevention of ulcer disease in addition to proton pump inhibitor maintenance therapy. Various studies brought further support for the hypothesis that H. pylori eradication is of some benefit for patients with non-ulcer dyspepsia, although the effects are limited. The prevalence of H. pylori is lower among GERD patients than among controls, but H. pylori eradication has not been consistently shown to increase the risk for the newly development of GERD in an individual subject undergoing H. pylori eradication. The discussion on H. pylori and GERD should not preclude us from treating H. pylori-infected patients for accepted clinical indications. In patients using proton pump inhibitors for GERD, H. pylori eradication leads to a resolution of their corpus-predominant pangastritis, without impairing the efficacy of PPI therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1083-4389.2004.00247.x
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  • 3
    Electronic Resource
    Electronic Resource
    The Functional Status of the Helicobacter pylori sabB Adhesin Gene as a Putative Marker for Disease Outcome (2004)
    Oxford, UK : Blackwell Science Ltd
    Helicobacter 9 (2004), S. 0 
    Details
    ISSN: 1523-5378
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background.  Helicobacter pylori factors that contribute to disease outcome are largely unknown, but intimate contact with host cells mediated by outer membrane proteins is thought to play an important role. Expression of the outer membrane proteins OipA, HopZ, SabA, and SabB is regulated by phase-variable dinucleotide repeats in the coding regions of the respective genes. We have evaluated the correlation between the expression status of these four genes and disease outcome of H. pylori infection in a Dutch patient population.Materials and Methods.  H. pylori strains, isolated from 96 Dutch patients with gastritis (n = 29), duodenal ulcer (n = 28), gastric ulcer (n = 21), gastric carcinoma (n = 9), and lymphoma (n = 9), were analyzed for the ‘on/off’ expression status of the H. pylori genes oipA, hopZ, sabA, and sabB by direct DNA sequence analysis of amplified fragments.Results.  The off-status of sabB was significantly associated with duodenal ulcer (p = .036), but not with gastric ulcer. In contrast, the expression status of oipA, hopZ, and sabA did not correlate with disease outcome. Furthermore, lymphoma strains appeared to express a significantly smaller amount of putative adhesins when compared to gastritis, gastric ulcer, duodenal ulcer and gastric carcinoma strains (p 〈 .02 for all groups tested).Conclusion.  The off-status of sabB was found to be associated with duodenal ulcer disease, and thus represents a putative marker for disease outcome. Assuming that SabB is involved in bacterial adhesion, this association suggests that adherent H. pylori are more prone to elimination by the host immune system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1083-4389.2004.00213.x
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  • 4
    Electronic Resource
    Electronic Resource
    The Role of the Ferric Uptake Regulator (Fur) in Regulation of Helicobacter pylori Iron Uptake (2002)
    Oxford, UK : Blackwell Science Ltd
    Helicobacter 7 (2002), S. 0 
    Details
    ISSN: 1523-5378
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background. Availability of the essential nutrient iron is thought to vary greatly in the gastric mucosa, and thus the human gastric pathogen Helicobacter pylori requires regulatory responses to these environmental changes. Bacterial iron-responsive regulation is often mediated by Ferric Uptake Regulator (Fur) homologs, and in this study we have determined the role of H. pylori Fur in regulation of H. pylori iron uptake.Methods. Wild-type H. pylori and fur mutant derivatives were compared after growth in iron-restricted and iron-replete conditions. Iron-uptake was measured using 55Fe-labeled iron, whereas gene expression was monitored at the transcriptional level using Northern hybridization and lacZ reporter gene fusions.Results. Iron-uptake and total cellular iron content were approximately five-fold increased in the fur mutant compared with the wild-type strain, which indicated that in the fur mutant iron-uptake is not repressed by excess iron. A comprehensive screening of all H. pylori genes encoding putative iron-uptake proteins indicated that some of these H. pylori genes are constitutively expressed, while others are iron- and Fur-regulated.Conclusions. Iron uptake in H. pylori is in part differently regulated compared with other bacteria, since in H. pylori some iron-uptake systems are constitutively expressed. However, other iron uptake systems of H. pylori display the iron- and Fur-mediated repression that is common in bacteria. Taken together, this Fur-mediated modulation of iron-uptake capacity may be a specific adaptation to the conditions in the human stomach, where iron starvation and iron overload can be encountered in relatively short time intervals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1523-5378.2002.00088.x
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  • 5
    Electronic Resource
    Electronic Resource
    Identification of Environmental Stress-Regulated Genes in Helicobacter pylori by a lacZ Reporter Gene Fusion System (2001)
    Oxford, UK : Blackwell Science Ltd
    Helicobacter 6 (2001), S. 0 
    Details
    ISSN: 1523-5378
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Helicobacter pylori persists in the human stomach for decades. This requires an efficient adaptation of H. pylori to the gastric niche and involves the regulation of bacterial genes in response to environmental stress. Efficient molecular tools to identify regulated H. pylori genes are scarce, therefore we developed a genomic lacZ reporter gene fusion system in H. pylori to screen for stress-regulated genes.〈section xml:id="abs1-3"〉〈title type="main"〉Materials and methods.The integration vector pBW was constructed and used to generate random genomic lacZ fusions in H. pylori. Two-hundred-and-fifty H. pylori transformants were selected from this library, replica-plated and screened for differential lacZ expression after exposure to two environmental stress conditions: increased temperature (42°C), and iron-limitation.〈section xml:id="abs1-4"〉〈title type="main"〉Results.From a library of H. pylori transformants with random genomic transcriptional lacZ fusions, two stress-regulated H. pylori loci were identified. The transcription of a gene of unknown function (designated hsp12) was increased by incubation at 42°C. The transcription of a locus, consisting of the three fumarate reductase subunit genes (frdCAB) and the HP0190 gene from H. pylori strain 26695, was decreased under iron-limitation.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions.This is the first time that a genomic transcriptional lacZ reporter gene H. pylori library has been used as a tool for the fast and efficient identification of environmental stress-regulated H. pylori genes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1083-4389.2001.00046.x
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  • 6
    Electronic Resource
    Electronic Resource
    The dprA gene is required for natural transformation of Helicobacter pylori (2000)
    Oxford, UK : Blackwell Publishing Ltd
    FEMS immunology and medical microbiology 27 (2000), S. 0 
    Details
    ISSN: 1574-695X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Genetic recombination in Helicobacter pylori is believed to be involved in host adaptation of this gastric pathogen and uptake of DNA by natural transformation can result in changes in virulence factors as well as antigenic variation. To elucidate the mechanisms involved in natural transformation we tested two genes with homology to known competence genes (dprA and traG) for their role in this process. Insertion mutants in these genes were constructed in two different H. pylori strains and their competence by natural transformation was compared to the wild-type. Mutation of the traG homolog did not reduce competence. Mutation of the dprA gene, however, severely impaired natural transformation both with plasmid and chromosomal DNA. Our data indicate that dprA and comB3 are essential parts of a common pathway for chromosomal and plasmid transformation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1574-695X.2000.tb01418.x
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  • 7
    Electronic Resource
    Electronic Resource
    The stress-induced hsp12 gene shows genetic variation among Helicobacter pylori strains (2003)
    Oxford, UK : Blackwell Publishing Ltd
    FEMS immunology and medical microbiology 38 (2003), S. 0 
    Details
    ISSN: 1574-695X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The transcriptional regulation, genetic variation and clinical relevance of the strain-specific hsp12 gene of the human gastric pathogen Helicobacter pylori were investigated. Although the transcription of the hsp12 gene in H. pylori strain 1061 was induced by growth under iron-, pH- and temperature-stress conditions, the gene was not essential for growth under these stress conditions. The locus containing the hsp12 gene showed considerable genetic variation. A total of eight different strain-specific alleles were identified, of which three are mosaic variants of the hsp12 gene and five that are unrelated to the hsp12 gene. The hsp12 locus of six paired sets of strains obtained from patients with 7–10-year time intervals remained unaltered, indicating that genetic variation does not occur during chronic infection. No significant association was found between the presence of a hsp12 gene and peptic ulcer disease in clinical isolates obtained from 26 patients. The stress-regulated, strain-specific hsp12 genes may be involved in adaptation of individual H. pylori strains to their specific hosts, and contribute to long-term colonization of the gastric niche.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/S0928-8244(03)00105-6
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  • 8
    Electronic Resource
    Electronic Resource
    IgG antibody titer against Helicobacter pylori correlates with presence of cytotoxin associated gene A-positive H. pylori strains (2000)
    Oxford, UK : Blackwell Publishing Ltd
    FEMS immunology and medical microbiology 28 (2000), S. 0 
    Details
    ISSN: 1574-695X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The level of the IgG antibody titer against Helicobacter pylori correlates with the severity of gastritis. H. pylori strains can harbor the so-called pathogenicity island, containing the cytotoxin associated gene (cagA). Since cagA-positive strains are more virulent it can be postulated that the gastritis will be more severe and hence the IgG antibody titer higher. In a cross-sectional study the correlation of IgG antibody titer and cagA status was studied from patients undergoing upper gastrointestinal endoscopy. Biopsy specimens were obtained to determine the H. pylori status. In addition a serum sample was taken for detection of IgG antibodies against H. pylori as well as CagA. A total of 290 patients positive for IgG antibodies against H. pylori were included. Of these 153 were cagA-positive and 137 were cagA-negative. The mean IgG antibody titer was significantly higher in cagA-positive patients compared to cagA-negatives, 0.75 (S.D. 0.22) versus 0.69 (S.D. 0.24) (P=0.033). It is concluded that the IgG antibody titer is significantly higher in patients harboring cagA-positive H. pylori strains. However, in daily practice the level in IgG antibody titer cannot predict whether or not an individual carries a cagA-positive H. pylori strain since major overlap in IgG antibody titer between cagA-positive and cagA-negative patients is present.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1574-695X.2000.tb01468.x
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  • 9
    Electronic Resource
    Electronic Resource
    Detection of high-level tetracycline resistance in clinical isolates of Helicobacter pylori using PCR-RFLP (2004)
    Oxford, UK : Blackwell Publishing Ltd
    FEMS immunology and medical microbiology 40 (2004), S. 0 
    Details
    ISSN: 1574-695X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Tetracycline is one of four antibiotics commonly used for the treatment of Helicobacter pylori infection, but its effectiveness is decreasing as the incidence of tetracycline resistance is increasing. In five Brazilian tetracycline-resistant (TetR) H. pylori isolates, high-level tetracycline resistance is mediated by the triple-base-pair substitution AGA926–928→TTC in both 16S rRNA genes, as was previously observed in two independent high-level TetRH. pylori strains. A polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) assay was developed for the detection of the AGA926–928→TTC substitution, and confirmed the presence of the aforementioned triple-base-pair substitution in all five Brazilian TetR isolates. This PCR-RFLP-based approach distinguishes the high-level TetR isolates from low-level TetR and TetSH. pylori strains and thus allows the direct detection of TetRH. pylori isolates.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/S0928-8244(03)00277-3
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  • 10
    Electronic Resource
    Electronic Resource
    The Helicobacter pylori plasticity region locus jhp0947–jhp0949 is associated with duodenal ulcer disease and interleukin-12 production in monocyte cells (2004)
    Oxford, UK : Blackwell Publishing Ltd
    FEMS immunology and medical microbiology 41 (2004), S. 0 
    Details
    ISSN: 1574-695X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Colonization with Helicobacter pylori always results in chronic gastritis, which is controlled by infiltration of mononuclear cells and the subsequent release of cytokines like interleukin (IL)-12. To identify H. pylori factors involved in inducing cytokine production in mononuclear cells, a random H. pylori mutant library was screened for the inability to induce IL-12 production in monocyte THP-1 cells. Of the 231 random mutants screened, one mutant (M1) showed a consistent twofold decrease in the amount of IL-12 induction compared to the parental strain 1061 (P〈0.01). Further characterization of mutant M1 revealed that the kanamycin resistance cassette had integrated in the jhp0945 gene, which is situated in an H. pylori strain-specific plasticity region. Three reference strains possessing this plasticity region induced significantly higher amounts of IL-12 when compared to the H. pylori 26695 reference strain, which does not possess this plasticity region. The role in disease outcome of jhp0945 as well as the neighbouring plasticity region genes jhp0947 and jhp049 was assessed in a Dutch population cohort. Firstly, the presence of jhp0947 was completely linked with that of jhp0949 and was roughly associated with jhp0945 (P=0.072), but not with the cag pathogenicity island (PAI) (P=0.464). The presence of the jhp0947 and jhp0949 genes, but not of jhp0945, was significantly associated with duodenal ulcer disease when compared to gastritis (P=0.027). Therefore, the jhp0947–jhp0949 locus may be a novel putative H. pylori marker for disease outcome independent of the cag PAI.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/j.femsim.2004.03.003
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