scholarly journals Effect of FliK mutation on the transcriptional activity of the σ 54 sigma factor RpoN in Helicobacter pylori

Microbiology ◽  
2009 ◽  
Vol 155 (6) ◽  
pp. 1901-1911 ◽  
Author(s):  
Francois P. Douillard ◽  
Kieran A. Ryan ◽  
Jason Hinds ◽  
Paul W. O'Toole
Keyword(s):  
Helicobacter Pylori ◽  
Sigma Factor ◽  
Transcriptional Activity ◽  
Human Gastric Mucosa ◽  
Hook Length ◽  
Altered Expression ◽  
Flagellar Assembly ◽  
Gene Regulatory ◽  
H Pylori ◽  
And Control

Helicobacter pylori is a motile Gram-negative bacterium that colonizes and persists in the human gastric mucosa. The flagellum gene regulatory circuitry of H. pylori is unique in many aspects compared with the Salmonella/Escherichia coli paradigms, and some regulatory checkpoints remain unclear. FliK controls the hook length during flagellar assembly. Microarray analysis of a fliK-null mutant revealed increased transcription of genes under the control of the σ 54 sigma factor RpoN. This sigma factor has been shown to be responsible for transcription of the class II flagellar genes, including flgE and flaB. No genes higher in the flagellar hierarchy had altered expression, suggesting specific and localized FliK-dependent feedback on the RpoN regulon. FliK thus appears to be involved in three processes: hook-length control, export substrate specificity and control of RpoN transcriptional activity.

Helicobacter pylori (H. pylori) infection increases IL-8 and IL-6 production from human gastric mucosa

1995 ◽  
Vol 108 (4) ◽  
pp. A769
Author(s):  
T. Ando ◽  
K. Kusugami ◽  
M. Sakakibara ◽  
T. Shimizu ◽  
M. Shinoda ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Human Gastric Mucosa ◽  
H Pylori

scholarly journals Therapeutic Vaccination against Helicobacter pylori in the Beagle Dog Experimental Model: Safety, Immunogenicity, and Efficacy

2004 ◽  
Vol 72 (6) ◽  
pp. 3252-3259 ◽  
Author(s):  
Giacomo Rossi ◽  
Paolo Ruggiero ◽  
Samuele Peppoloni ◽  
Laura Pancotto ◽  
Damiano Fortuna ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Bacterial Colonization ◽  
Human Infection ◽  
Human Gastric Mucosa ◽  
Therapeutic Vaccination ◽  
Beagle Dogs ◽  
Beagle Dog ◽  
Vaccine Approach ◽  
H Pylori ◽  
Different Doses

ABSTRACT Helicobacter pylori is a gram-negative bacterium that colonizes the human gastric mucosa causing gastritis and peptic ulcer and increasing the risk of gastric cancer. The efficacy of current antibiotic-based therapies can be limited by problems of patient compliance and increasing antibiotic resistance; the vaccine approach can overcome these limits. The present study describes the therapeutic vaccination of experimentally H. pylori-infected beagle dogs, an animal model that reproduces several aspects of the human infection with H. pylori. The vaccine consisted of three recombinant H. pylori antigens, CagA, VacA, and NAP, formulated at different doses (10, 25, or 50 μg each) with alum and administered intramuscularly either weekly or monthly. No adverse effects were observed after vaccination and a good immunoglobulin G response was generated against each of the three antigens. Bacterial colonization and gastritis were decreased after the completion of the vaccination cycle, especially in the case of the monthly immunization schedule. In conclusion, therapeutic vaccination in the beagle dog model was safe and immunogenic and was able to limit H. pylori colonization and the related gastric pathology.

scholarly journals Helicobacter pylori–binding nonacid glycosphingolipids in the human stomach

2018 ◽  
Vol 293 (44) ◽  
pp. 17248-17266 ◽  
Author(s):  
Chunsheng Jin ◽  
Angela Barone ◽  
Thomas Borén ◽  
Susann Teneberg
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Structural Complexity ◽  
Human Stomach ◽  
Carbohydrate Binding ◽  
Human Gastric Mucosa ◽  
H Pylori ◽  
Contrast Information

Helicobacter pylori has a number of well-characterized carbohydrate-binding adhesins (BabA, SabA, and LabA) that promote adhesion to the gastric mucosa. In contrast, information on the glycoconjugates present in the human stomach remains unavailable. Here, we used MS and binding of carbohydrate-recognizing ligands to characterize the glycosphingolipids of three human stomachs from individuals with different blood group phenotypes (O(Rh−)P, A(Rh+)P, and A(Rh+)p), focusing on compounds recognized by H. pylori. We observed a high degree of structural complexity, and the composition of glycosphingolipids differed among individuals with different blood groups. The type 2 chain was the dominating core chain of the complex glycosphingolipids in the human stomach, in contrast to the complex glycosphingolipids in the human small intestine, which have mainly a type 1 core. H. pylori did not bind to the O(Rh−)P stomach glycosphingolipids, whose major complex glycosphingolipids were neolactotetraosylceramide, the Lex, Lea, and H type 2 pentaosylceramides, and the Ley hexaosylceramide. Several H. pylori-binding compounds were present among the A(Rh+)P and A(Rh+)p stomach glycosphingolipids. Ligands for BabA-mediated binding of H. pylori were the Leb hexaosylceramide, the H type 1 pentaosylceramide, and the A type 1/ALeb heptaosylceramide. Additional H. pylori-binding glycosphingolipids recognized by BabA-deficient strains were lactosylceramide, lactotetraosylceramide, the x2 pentaosylceramide, and neolactohexaosylceramide. Our characterization of human gastric receptors required for H. pylori adhesion provides a basis for the development of specific compounds that inhibit the binding of this bacterium to the human gastric mucosa.

Seroprevalence of Helicobacter pylori infection in patients with chronic nonspecific pharyngitis: preliminary study

2007 ◽  
Vol 122 (1) ◽  
pp. 61-64 ◽  
Author(s):  
İ Aladag ◽  
Y Bulut ◽  
M Guven ◽  
A Eyibilen ◽  
K Yelken
Keyword(s):  
Helicobacter Pylori ◽  
Treatment Strategies ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Control Groups ◽  
Chi Square ◽  
Control Subjects ◽  
The Difference ◽  
H Pylori ◽  
And Control

AbstractBackground and objectives:Chronic nonspecific pharyngitis is a chronic inflammation of the pharynx. It is found worldwide, and treatment is difficult. The underlying aetiopathogenesis is still controversial. The aim of this study was to investigate Helicobacter pylori seroprevalence in chronic nonspecific pharyngitis patients without other possible causative factors for chronic pharyngeal irritation and without H pylori gastric mucosal infection.Materials and methods:Forty-one patients with symptoms of chronic nonspecific pharyngitis and 30 healthy control subjects were enrolled in this prospective, controlled, clinical study. In both study and control groups, selected patients were shown to have gastric mucosa uninfected by H pylori, as demonstrated by the 14C-urea breath test. Comprehensive otorhinolaryngological examination did not elicit any factor contributing to the chronic pharyngeal complaint. Serum H pylori immunoglobulin G antibody titres were assayed using serum enzyme-linked immunosorbent assay. The difference between the study and control groups was analysed by the chi-square test (the likelihood ratio was used).Results:Thirty-two of the 41 patients (78 per cent) and 14 of the 30 control subjects (46.7 per cent) were found to be H pylori positive. Patients with chronic nonspecific pharyngitis were found to have a significantly higher rate of H pylori seropositivity than the control group (p = 0.016).Conclusion:These data may be important in developing future treatment strategies for chronic nonspecific pharyngitis.

scholarly journals Helicobacter pylori FlhB Function: the FlhB C-Terminal Homologue HP1575 Acts as a “Spare Part” To Permit Flagellar Export When the HP0770 FlhBCC Domain Is Deleted

2006 ◽  
Vol 188 (21) ◽  
pp. 7531-7541 ◽  
Author(s):  
Matthew E. Wand ◽  
R. Elizabeth Sockett ◽  
Katy J. Evans ◽  
Neil Doherty ◽  
Paul M. Sharp ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Spare Part ◽  
Significant Similarity ◽  
Flagellar Assembly ◽  
Processing Event ◽  
Processing Site ◽  
Flagellar Protein ◽  
H Pylori ◽  
Export Protein

ABSTRACT In Helicobacter pylori 26695, a gene annotated HP1575 encodes a putative protein of unknown function which shows significant similarity to part of the C-terminal domain of the flagellar export protein FlhB. In Salmonella enterica, this part (FlhBCC) is proteolytically cleaved from the full-length FlhB, a processing event that is required for flagellar protein export and, thus, motility. The role of FlhB (HP0770) and its C-terminal homologue HP1575 was studied in H. pylori using a range of nonpolar deletion mutants defective in HP1575, HP0770, and the CC domain of HP0770 (HP0770CC). Deletion of HP0770 abolished swimming motility, whereas mutants carrying a deletion of either HP1575 or HP0770CC retained their ability to swim. An H. pylori strain containing deletions in both HP1575 and HP0770CC was nonmotile and did not produce flagella, suggesting that at least one of the two proteins had to be present for flagellar assembly to occur. Indeed, motility was restored when HP1575 was reintroduced into this strain immediately downstream of, but not fused to, the truncated HP0770 gene. Thus, HP1575 can functionally replace HP0770CC in this background. Like FlhB in S. enterica, HP0770 appeared to be proteolytically processed at a conserved NPTH processing site. However, mutation of the proline contained within the NPTH site of HP0770 did not affect motility and flagellar assembly, although it clearly interfered with processing when the protein was heterologously produced in Escherichia coli.

scholarly journals Gene structure of the Helicobacter pylori cytotoxin and evidence of its key role in gastric disease.

1994 ◽  
Vol 179 (5) ◽  
pp. 1653-1658 ◽  
Author(s):  
J L Telford ◽  
P Ghiara ◽  
M Dell'Orco ◽  
M Comanducci ◽  
D Burroni ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Peptic Ulcer ◽  
Gastric Mucosa ◽  
Chronic Infection ◽  
Gastric Disease ◽  
Human Gastric Mucosa ◽  
Gastric Lesions ◽  
Gram Negative ◽  
H Pylori ◽  
Cytotoxin Gene

The gram negative, microaerophilic bacterium Helicobacter pylori colonizes the human gastric mucosa and establishes a chronic infection that is tightly associated with atrophic gastritis, peptic ulcer, and gastric carcinoma. Cloning of the H. pylori cytotoxin gene shows that the protein is synthesized as a 140-kD precursor that is processed to a 94-kD fully active toxin. Oral administration to mice of the purified 94-kD protein caused ulceration and gastric lesions that bear some similarities to the pathology observed in humans. The cloning of the cytotoxin gene and the development of a mouse model of human gastric disease will provide the basis for the understanding of H. pylori pathogenesis and the development of therapeutics and vaccines.

scholarly journals Helicobacter pylori Flagellar Hook-Filament Transition Is Controlled by a FliK Functional Homolog Encoded by the Gene HP0906

2005 ◽  
Vol 187 (16) ◽  
pp. 5742-5750 ◽  
Author(s):  
Kieran A. Ryan ◽  
Najma Karim ◽  
Mulugeta Worku ◽  
Charles W. Penn ◽  
Paul W. O'Toole
Keyword(s):  
Helicobacter Pylori ◽  
Enteric Bacteria ◽  
Hook Length ◽  
Chloramphenicol Resistance ◽  
Functional Homolog ◽  
Flagellar Proteins ◽  
H Pylori ◽  
Flagellar Biogenesis ◽  
Control Protein ◽  
Flagellar Genes

ABSTRACT Helicobacter pylori is a human gastric pathogen which is dependent on motility for infection. The H. pylori genome encodes a near-complete complement of flagellar proteins compared to model enteric bacteria. One of the few flagellar genes not annotated in H. pylori is that encoding FliK, a hook length control protein whose absence leads to a polyhook phenotype in Salmonella enterica. We investigated the role of the H. pylori gene HP0906 in flagellar biogenesis because of linkage to other flagellar genes, because of its transcriptional regulation pattern, and because of the properties of an ortholog in Campylobacter jejuni (N. Kamal and C. W. Penn, unpublished data). A nonpolar mutation of HP0906 in strain CCUG 17874 was generated by insertion of a chloramphenicol resistance marker. Cells of the mutant were almost completely nonmotile but produced sheathed, undulating polyhook structures at the cell pole. Expression of HP0906 in a Salmonella fliK mutant restored motility, confirming that HP0906 is the H. pylori fliK gene. Mutation of HP0906 caused a dramatic reduction in H. pylori flagellin protein production and a significant increase in production of the hook protein FlgE. The HP0906 mutant showed increased transcription of the flgE and flaB genes relative to the wild type, down-regulation of flaA transcription, and no significant change in transcription of the flagellar intermediate class genes flgM, fliD, and flhA. We conclude that the H. pylori HP0906 gene product is the hook length control protein FliK and that its function is required for turning off the σ54 regulon during progression of the flagellar gene expression cascade.

scholarly journals Helicobacter pylori Membrane Vesicles Stimulate Innate Pro- and Anti-Inflammatory Responses and Induce Apoptosis in Jurkat T Cells

2014 ◽  
Vol 82 (4) ◽  
pp. 1372-1381 ◽  
Author(s):  
Jody Winter ◽  
Darren Letley ◽  
Joanne Rhead ◽  
John Atherton ◽  
Karen Robinson
Keyword(s):  
Helicobacter Pylori ◽  
T Cell ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Membrane Vesicles ◽  
Human Gastric Mucosa ◽  
Content Type ◽  
Toxin Content ◽  
Anti Inflammatory ◽  
H Pylori

ABSTRACTPersistentHelicobacter pyloriinfection induces chronic inflammation in the human gastric mucosa, which is associated with development of peptic ulceration, gastric atrophy, and gastric adenocarcinoma. It has been postulated that secretion of immunomodulatory molecules byH. pylorifacilitates bacterial persistence, and membrane vesicles (MV), which have the potential to cross the gastric epithelial barrier, may mediate delivery of these molecules to host immune cells. However, bacterial MV effects on human immune cells remain largely uncharacterized to date. In the present study, we investigated the immunomodulatory effects ofH. pyloriMV with and without the vacuolating cytotoxin, VacA, which inhibits human T cell activity. We show a high degree of variability in the toxin content of vesicles between twoH. pyloristrains (SS1 and 60190). Vesicles from the more toxigenic 60190 strain contain more VacA (s1i1 type) than vesicles from the SS1 strain (s2i2 VacA), but engineering the SS1 strain to produce s1i1 VacA did not increase the toxin content of its vesicles. Vesicles from all strains tested, including a 60190 isogenic mutant null for VacA, strongly induced interleukin-10 (IL-10) and IL-6 production by human peripheral blood mononuclear cells independently of the infection status of the donor. Finally, we show thatH. pyloriMV induce T cell apoptosis and that this is enhanced by, but not completely dependent on, the carriage of VacA. Together, these findings suggest a role forH. pyloriMV in the stimulation of innate pro- and anti-inflammatory responses and in the suppression of T cell immunity.

scholarly journals Downregulation of Interleukin- (IL-) 17 through Enhanced Indoleamine 2,3-Dioxygenase (IDO) Induction by Curcumin: A Potential Mechanism of Tolerance towards Helicobacter pylori

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Tiziana Larussa ◽  
Serena Gervasi ◽  
Rita Liparoti ◽  
Evelina Suraci ◽  
Raffaella Marasco ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Antimicrobial Properties ◽  
Human Gastric Mucosa ◽  
T Cell Apoptosis ◽  
Indoleamine 2,3 Dioxygenase ◽  
Treated Sample ◽  
Tryptophan Catabolism ◽  
Gastric Biopsies ◽  
H Pylori

The anti-inflammatory and antimicrobial properties of curcumin suggest its use as an anti-Helicobacter pylori (H. pylori) agent, but mechanisms underlying its helpful activity are still not clear. Indoleamine 2,3-dioxygenase (IDO) promotes the effector T cell apoptosis by catalyzing the rate-limiting first step in tryptophan catabolism, and its high expression in H. pylori-infected human gastric mucosa attenuates Th1 and Th17 immune response. The aim of this study was to investigate the role of curcumin in modulating the expression of IL-17 and IDO in H. pylori-infected human gastric mucosa. In an organ culture chamber, gastric biopsies from 35 patients were treated with and without 200 μM curcumin. In H. pylori-infected patients (n=21), IL-17 was significantly lower, both in gastric biopsies (p=0.0003) and culture supernatant (p=0.0001) while IDO significantly increased (p<0.00001) in curcumin-treated sample compared with untreated samples. In a subgroup of H. pylori-infected patients (n=15), samples treated with curcumin in addition to IDO inhibitor 1-methyl-L-tryptophan (1-MT) showed a higher expression of IL-17 compared with untreated samples and curcumin-treated alone (p<0.00001). Curcumin downregulates IL-17 production through the induction of IDO in H. pylori-infected human gastric mucosa, suggesting its role in dampening H. pylori-induced immune-mediated inflammatory changes.

scholarly journals Interleukin-12 Drives the Th1 Signaling Pathway in Helicobacter pylori-Infected Human Gastric Mucosa

2007 ◽  
Vol 75 (4) ◽  
pp. 1738-1744 ◽  
Author(s):  
Antonia Pellicanò ◽  
Ladislava Sebkova ◽  
Giovanni Monteleone ◽  
Giovanni Guarnieri ◽  
Maria Imeneo ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Transcription Factors ◽  
Gastric Mucosa ◽  
Enzyme Linked Immunosorbent Assay ◽  
Human Gastric Mucosa ◽  
Organ Cultures ◽  
Gastric Biopsies ◽  
Ifn Γ ◽  
H Pylori ◽  
Cell Commitment

ABSTRACT In this study we examined mechanisms that regulate T-helper lymphocyte 1 (Th1) commitment in Helicobacter pylori-infected human gastric mucosa. The levels of gamma interferon (IFN-γ), interleukin-4 (IL-4), and IL-12 in total extracts of gastric biopsies taken from H. pylori-infected and uninfected patients were determined by an enzyme-linked immunosorbent assay. The levels of signal transducer and activator of transcription 4 (STAT4), STAT6, and T-box expressed in T cells (T-bet) in total proteins extracted from gastric biopsies were determined by Western blotting. Finally, the effect of a neutralizing IL-12 antibody on expression of Th1 transcription factors and the levels of IFN-γ in organ cultures of H. pylori-infected biopsies was examined. Increased levels of IFN-γ and IL-12 were found in gastric biopsy samples of H. pylori-infected patients compared to the levels in uninfected patients. In addition, H. pylori-infected biopsies exhibited high levels of expression of phosphorylated STAT4 and T-bet. Higher levels of IFN-γ and expression of Th1 transcription factors were associated with greater infiltration of mononuclear cells in the gastric mucosa. By contrast, production of IL-4 and expression of phosphorylated STAT6 were not associated with the intensity of mononuclear cell infiltration. In ex vivo organ cultures of H. pylori-infected biopsies, neutralization of endogenous IL-12 down-regulated the expression of phosphorylated STAT4 and T-bet and reduced IFN-γ production. Our data indicated that IL-12 contributes to the Th1 cell commitment in H. pylori-infected human gastric mucosa.

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