scholarly journals The Interaction of Helicobacter pylori with TFF1 and Its Role in Mediating the Tropism of the Bacteria Within the Stomach

2019 ◽  
Vol 20 (18) ◽  
pp. 4400 ◽  
Author(s):  
Marguerite Clyne ◽  
Felicity E. B. May
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucin ◽  
Carbohydrate Binding ◽  
Mucus Layer ◽  
Gastric Mucus ◽  
Core Oligosaccharide ◽  
Epithelial Surface ◽  
Hydrophobic Residues ◽  
H Pylori ◽  
Trefoil Factor 1

Helicobacter pylori colonises the human stomach and has tropism for the gastric mucin, MUC5AC. The majority of organisms live in the adherent mucus layer within their preferred location, close to the epithelial surface where the pH is near neutral. Trefoil factor 1 (TFF1) is a small trefoil protein co-expressed with the gastric mucin MUC5AC in surface foveolar cells and co-secreted with MUC5AC into gastric mucus. Helicobacter pylori binds with greater avidity to TFF1 dimer, which is present in gastric mucus, than to TFF1 monomer. Binding of H. pylori to TFF1 is mediated by the core oligosaccharide subunit of H. pylori lipopolysaccharide at pH 5.0–6.0. Treatment of H. pylori lipopolysaccharide with mannosidase or glucosidase inhibits its interaction with TFF1. Both TFF1 and H. pylori have a propensity for binding to mucins with terminal non-reducing α- or β-linked N-acetyl-d-glucosamine or α-(2,3) linked sialic acid or Gal-3-SO42−. These findings are strong evidence that TFF1 has carbohydrate-binding properties that may involve a conserved patch of aromatic hydrophobic residues on the surface of its trefoil domain. The pH-dependent lectin properties of TFF1 may serve to locate H. pylori deep in the gastric mucus layer close to the epithelium rather than at the epithelial surface. This restricted localisation could limit the interaction of H. pylori with epithelial cells and the subsequent host signalling events that promote inflammation.

scholarly journals Helicobacter pylori in vivo causes structural changes in the adherent gastric mucus layer but barrier thickness is not compromised

Gut ◽  
1998 ◽  
Vol 43 (4) ◽  
pp. 470-475 ◽  
Author(s):  
J L Newton ◽  
N Jordan ◽  
L Oliver ◽  
V Strugala ◽  
J Pearson ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Structural Changes ◽  
Endoscopic Biopsy ◽  
Gastric Atrophy ◽  
Mucus Layer ◽  
Gastric Mucus ◽  
Mucus Gel ◽  
Mucus Barrier ◽  
H Pylori

Background—It has been proposed that a pathogenic effect of Helicobacter pylori is a weakening of the protective mucus barrier; however, this remains controversial.Aims—To clarify the effects of H pylori infection on the mucus gel barrier in vivo.Methods—Mucus gel polymeric structure and the thickness of the adherent mucus barrier were measured in endoscopic biopsy samples in subjects with and without H pyloriinfection.Results—There was a significant 18% reduction in the proportion of polymeric gel forming mucin in the adherent mucus layer in H pylori positive compared with negative subjects. There was no change in the adherent mucus thickness betweenH pylori positive and negative subjects without gastric atrophy (mean (SD): 104 (26) μm, 106 (30) μm respectively). There was however a significant reduction in mucus thickness in those H pylori positive subjects with underlying gastric atrophy (84 (13) μm, p=0.03) compared with those without atrophy.Conclusions—A partial breakdown in gel forming structure of the gastric mucus barrier does occur in H pylori infection per se but this is insufficient to cause a collapse of the mucus barrier.

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.

scholarly journals In Vivo Distribution of Helicobacter felis in the Gastric Mucus of the Mouse: Experimental Method and Results

1999 ◽  
Vol 67 (10) ◽  
pp. 5151-5156 ◽  
Author(s):  
Sören Schreiber ◽  
Manuela Stüben ◽  
Christine Josenhans ◽  
Peter Scheid ◽  
Sebastian Suerbaum
Keyword(s):  
Bacterial Motility ◽  
Small Samples ◽  
Mucus Layer ◽  
Gastric Mucus ◽  
Epithelial Surface ◽  
Helicobacter Felis ◽  
Chemical Gradients ◽  
Tissue Surface ◽  
The Mean

ABSTRACT We describe a method that permits the collection of very small samples (2 nl) from precisely defined positions within the gastric mucus of anesthetized mice. This method was used to study the in vivo local distribution of bacteria within the mucus of Helicobacter felis-infected mice. A total of 200 samples from 40 mice were analyzed. Each sample was microscopically analyzed, within less than 1 min, as a native preparation. To avoid changes in bacterial location within the mucus after collection and to improve the counting accuracy, bacterial motility was blocked by adjusting the pH inside the collecting pipette to 4.5. The mucus in a collected sample was subdivided into three layers, an epithelial layer (the first 25 μm of mucus from the tissue-mucus interface), a luminal layer (the last 25 μm to the mucus-lumen interface), and the remaining central mucus layer. The volume of the analyzed segments in the sample was between 4 and 9 pl. The concentration of bacteria inside the epithelial mucus layer was 3,400 per nl, but it was only 50 per nl inside the central mucus layer. The mean distance of H. felis to the epithelial surface was 16 μm. A total of 75% of all H. felis bacteria resided in the mucus zone between 5 and 20 μm from the tissue surface, with no bacteria closer than 5 μm to the epithelial surface. This method permits the study of factors determining the density of colonization and distribution of bacteria along chemical gradients with a high precision.

Does Helicobacter pylori affect gastric mucin expression? Relationship between gastric antral mucin expression and H. pylori colonization

2001 ◽  
Vol 13 (1) ◽  
pp. 19-23 ◽  
Author(s):  
Sara Morgenstern ◽  
Rivka Koren ◽  
Steven F. Moss ◽  
Gerald Fraser ◽  
Eli Okon ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucin ◽  
Mucin Expression ◽  
H Pylori

scholarly journals Expression of the BabA Adhesin during Experimental Infection with Helicobacter pylori

2010 ◽  
Vol 78 (4) ◽  
pp. 1593-1600 ◽  
Author(s):  
Cathy M. Styer ◽  
Lori M. Hansen ◽  
Cara L. Cooke ◽  
Amy M. Gundersen ◽  
Sung Sook Choi ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Amino Acid ◽  
Experimental Infection ◽  
Stop Codon ◽  
Rhesus Macaques ◽  
Phase Variation ◽  
Amino Acid Residues ◽  
Epithelial Surface ◽  
H Pylori

ABSTRACT The Helicobacter pylori babA gene encodes an outer membrane protein that mediates binding to fucosylated ABH antigens of the ABO blood group. We recently demonstrated that BabA expression is lost during experimental infection of rhesus macaques with H. pylori J166. We sought to test the generality of this observation by comparison of different H. pylori strains and different animal hosts. Challenge of macaques with H. pylori J99 yielded output strains that lost BabA expression, either by selection and then expansion of a subpopulation of J99 that had a single-base-pair mutation that encoded a stop codon or by gene conversion of babA with a duplicate copy of babB, a paralog of unknown function. Challenge of mice with H. pylori J166, which unlike J99, has 5′ CT repeats in babA, resulted in loss of BabA expression due to phase variation. In the gerbil, Leb binding was lost by replacement of the babA gene that encoded Leb binding with a nonbinding allele that differed at six amino acid residues. Complementation experiments confirmed that change in these six amino acids of BabA was sufficient to eliminate binding to Leb and to gastric tissue. These results demonstrate that BabA expression in vivo is highly dynamic, and the findings implicate specific amino acid residues as critical for binding to fucosylated ABH antigens. We hypothesize that modification of BabA expression during H. pylori infection is a mechanism to adapt to changing conditions of inflammation and glycan expression at the epithelial surface.

scholarly journals Galectin-3 Plays an Important Role in Innate Immunity to Gastric Infection by Helicobacter pylori

2016 ◽  
Vol 84 (4) ◽  
pp. 1184-1193 ◽  
Author(s):  
Ah-Mee Park ◽  
Satoru Hagiwara ◽  
Daniel K. Hsu ◽  
Fu-Tong Liu ◽  
Osamu Yoshie
Keyword(s):  
Innate Immunity ◽  
Helicobacter Pylori ◽  
Bacterial Cells ◽  
Mucus Layer ◽  
Iodide Uptake ◽  
Gastric Glands ◽  
Content Type ◽  
Galectin 3 ◽  
H Pylori ◽  
Deficient Mice

We studied the role of galectin-3 (Gal3) in gastric infection byHelicobacter pylori. We first demonstrated that Gal3 was selectively expressed by gastric surface epithelial cells and abundantly secreted into the surface mucus layer. We next inoculatedH. pyloriSydney strain 1 into wild-type (WT) and Gal3-deficient mice using a stomach tube. At 2 weeks postinoculation, the bacterial cells were mostly trapped within the surface mucus layer in WT mice. In sharp contrast, they infiltrated deep into the gastric glands in Gal3-deficient mice. Bacterial loads in the gastric tissues were also much higher in Gal3-deficient mice than in WT mice. At 6 months postinoculation,H. pylorihad successfully colonized within the gastric glands of both WT and Gal3-deficient mice, although the bacterial loads were still higher in the latter. Furthermore, large lymphoid clusters mostly consisting of B cells were frequently observed in the gastric submucosa of Gal3-deficient mice.In vitro, peritoneal macrophages from Gal3-deficient mice were inefficient in killing engulfedH. pylori. Furthermore, recombinant Gal3 not only induced rapid aggregation ofH. pyloribut also exerted a potent bactericidal effect onH. pylorias revealed by propidium iodide uptake and a morphological shift from spiral to coccoid form. However, a minor fraction of bacterial cells, probably transient phase variants of Gal3-binding sugar moieties, escaped killing by Gal3. Collectively, our data demonstrate that Gal3 plays an important role in innate immunity to infection and colonization ofH. pylori.

scholarly journals Effect of proton pump inhibitor on the movement of Helicobacter pylori across the mucus layer to the gastric lumen

2019 ◽  
Author(s):  
shanshan Su(Former Corresponding Author) ◽  
Guo-qi Zheng(New Corresponding Author) ◽  
Ying-ying Liu ◽  
Yu-fei Liang ◽  
Hui Song ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Proton Pump Inhibitor ◽  
Gastric Juice ◽  
Proton Pump ◽  
Intervention Group ◽  
Control Group ◽  
Mucus Layer ◽  
Urease Test ◽  
Gastric Lumen ◽  
H Pylori

Abstract Background: Helicobacter pylori ( H. pylori ) cannot usually be detected in the gastric juice and it is thought that H. pylori may reside under the mucus layer for long term. The mechanisms of action of proton pump inhibitor (PPI)for H. pylori eradication are not entirely clear. Our study aimed to determine the role of PPI on the movement of H. pylori across the mucus layer to the gastric lumen and the mechanism of PPI on H. pylori eradication. Methods: Patients with H. pylori infection were intravenous injected with PPI (intervention group, n=31) or without PPI (control group, n=37). The presence of H. pylori in the gastric juice was evaluated by the rapid urease test (RUT), polymerase chain reaction (PCR), and culture methods. Results: The H. pylori positive detection rates were all significantly higher among patients in the intervention group than among patients in the control group by the RUT ( P < 0.0001), PCR ( P < 0.0001), and culturing ( P = 0.0386). Conclusion: H. pylori can penetrate across the mucus layer to the gastric lumen following PPI intervention, and thus it might represent a novel target in the eradication of H. pylori .

scholarly journals Identification of a d-glycero-d-manno-Heptosyltransferase Gene from Helicobacter pylori

2005 ◽  
Vol 187 (15) ◽  
pp. 5156-5165 ◽  
Author(s):  
Koji Hiratsuka ◽  
Susan M. Logan ◽  
J. Wayne Conlan ◽  
Vandana Chandan ◽  
Annie Aubry ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Critical Role ◽  
Outer Core ◽  
Core Region ◽  
Wild Type ◽  
Core Oligosaccharide ◽  
Detailed Structural Analysis ◽  
Insertional Inactivation ◽  
H Pylori

ABSTRACT We have identified a Helicobacter pylori d-glycero-d-manno-heptosyltransferase gene, HP0479, which is involved in the biosynthesis of the outer core region of H. pylori lipopolysaccharide (LPS). Insertional inactivation of HP0479 resulted in formation of a truncated LPS molecule lacking an α-1,6-glucan-, dd-heptose-containing outer core region and O-chain polysaccharide. Detailed structural analysis of purified LPS from HP0479 mutants of strains SS1, 26695, O:3, and PJ1 by a combination of chemical and mass spectrometric methods showed that HP0479 likely encodes α-1,2-d-glycero-d-manno-heptosyltransferase, which adds a d-glycero-d-manno-heptose residue (DDHepII) to a distal dd-heptose of the core oligosaccharide backbone of H. pylori LPS. When the wild-type HP0479 gene was reintegrated into the chromosome of strain 26695 by using an “antibiotic cassette swapping” method, the complete LPS structure was restored. Introduction of the HP0479 mutation into the H. pylori mouse-colonizing Sydney (SS1) strain and the clinical isolate PJ1, which expresses dd-heptoglycan, resulted in the loss of colonization in a mouse model. This indicates that H. pylori expressing a deeply truncated LPS is unable to successfully colonize the murine stomach and provides evidence for a critical role of the outer core region of H. pylori LPS in colonization.

scholarly journals Kinetics and Mechanisms of Extracellular Protein Release by Helicobacter pylori

1999 ◽  
Vol 67 (10) ◽  
pp. 5247-5252 ◽  
Author(s):  
Wayne Schraw ◽  
Mark S. McClain ◽  
Timothy L. Cover
Keyword(s):  
Helicobacter Pylori ◽  
Early Time ◽  
Medium Composition ◽  
Protein Release ◽  
Extracellular Protein ◽  
Broth Culture ◽  
Bacterial Cells ◽  
Gastric Mucus ◽  
Extracellular Release ◽  
H Pylori

ABSTRACT To investigate the kinetics and mechanisms of extracellular protein release by Helicobacter pylori, we analyzed the entry of metabolically radiolabeled bacterial proteins into broth culture supernatant. At early time points, vacuolating cytotoxin (VacA) constituted a major extracellular protein. Subsequently, culture supernatants accumulated many proteins that were components of intact bacterial cells. This nonselective release of proteins was associated with a decreasing turbidity of cultures and loss of bacterial viability, indicative of an autolytic process. The rates of VacA secretion and autolysis were each influenced by medium composition, and therefore these may be regulated phenomena. Extracellular release of proteins by H. pylori may be an important adaptation that facilitates the persistence of H. pylori in the human gastric mucus layer. Moreover, entry of proinflammatory proteins into the gastric mucosa may contribute to the induction of a mucosal inflammatory response.

A physics-based model for maintenance of the pH gradient in the gastric mucus layer

2017 ◽  
Vol 313 (6) ◽  
pp. G599-G612 ◽  
Author(s):  
Owen L. Lewis ◽  
James P. Keener ◽  
Aaron L. Fogelson
Keyword(s):  
Mucosal Surface ◽  
Ph Gradient ◽  
Model Parameters ◽  
Regulation Mechanism ◽  
Mucus Layer ◽  
Gastric Mucus ◽  
Epithelial Surface ◽  
Ph Gradients ◽  
Protective Function ◽  
The Face

It is generally accepted that the gastric mucus layer provides a protective barrier between the lumen and the mucosa, shielding the mucosa from acid and digestive enzymes and preventing autodigestion of the stomach epithelium. However, the precise mechanisms that contribute to this protective function are still up for debate. In particular, it is not clear what physical processes are responsible for transporting hydrogen protons, secreted within the gastric pits, across the mucus layer to the lumen without acidifying the environment adjacent to the epithelium. One hypothesis is that hydrogen may be bound to the mucin polymers themselves as they are convected away from the mucosal surface and eventually degraded in the stomach lumen. It is also not clear what mechanisms prevent hydrogen from diffusing back toward the mucosal surface, thereby lowering the local pH. In this work we investigate a physics-based model of ion transport within the mucosal layer based on a Nernst-Planck-like equation. Analysis of this model shows that the mechanism of transporting protons bound to the mucus gel is capable of reproducing the trans-mucus pH gradients reported in the literature. Furthermore, when coupled with ion exchange at the epithelial surface, our analysis shows that bicarbonate secretion alone is capable of neutralizing the epithelial pH, even in the face of enormous diffusive gradients of hydrogen. Maintenance of the pH gradient is found to be robust to a wide array of perturbations in both physiological and phenomenological model parameters, suggesting a robust physiological control mechanism. NEW & NOTEWORTHY This work combines modeling techniques based on physical principles, as well as novel numerical simulations to test the plausibility of one hypothesized mechanism for proton transport across the gastric mucus layer. Results show that this mechanism is able to maintain the extreme pH gradient seen in in vivo experiments and suggests a highly robust regulation mechanism to maintain this gradient in the face of dynamic lumen composition.

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