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 Adhesion of Helicobacter Species to the Human Gastric Mucosa: A Deep Look Into Glycans Role

2021 ◽  
Vol 8 ◽  
Author(s):  
Rita Matos ◽  
Irina Amorim ◽  
Ana Magalhães ◽  
Freddy Haesebrouck ◽  
Fátima Gärtner ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Human Stomach ◽  
Gastric Disease ◽  
Human Gastric Mucosa ◽  
Peptic Ulcers ◽  
Epithelial Surface ◽  
Natural Hosts ◽  
Glycan Receptors ◽  
H Pylori

Helicobacter species infections may be associated with the development of gastric disorders, such as gastritis, peptic ulcers, intestinal metaplasia, dysplasia and gastric carcinoma. Binding of these bacteria to the gastric mucosa occurs through the recognition of specific glycan receptors expressed by the host epithelial cells. This review addresses the state of the art knowledge on these host glycan structures and the bacterial adhesins involved in Helicobacter spp. adhesion to gastric mucosa colonization. Glycans are expressed on every cell surface and they are crucial for several biological processes, including protein folding, cell signaling and recognition, and host-pathogen interactions. Helicobacter pylori is the most predominant gastric Helicobacter species in humans. The adhesion of this bacterium to glycan epitopes present on the gastric epithelial surface is a crucial step for a successful colonization. Major adhesins essential for colonization and infection are the blood-group antigen-binding adhesin (BabA) which mediates the interaction with fucosylated H-type 1 and Lewis B glycans, and the sialic acid-binding adhesin (SabA) which recognizes the sialyl-Lewis A and X glycan antigens. Since not every H. pylori strain expresses functional BabA or SabA adhesins, other bacterial proteins are most probably also involved in this adhesion process, including LabA (LacdiNAc-binding adhesin), which binds to the LacdiNAc motif on MUC5AC mucin. Besides H. pylori, several other gastric non-Helicobacter pylori Helicobacters (NHPH), mainly associated with pigs (H. suis) and pets (H. felis, H. bizzozeronii, H. salomonis, and H. heilmannii), may also colonize the human stomach and cause gastric disease, including gastritis, peptic ulcers and mucosa-associated lymphoid tissue (MALT) lymphoma. These NHPH lack homologous to the major known adhesins involved in colonization of the human stomach. In humans, NHPH infection rate is much lower than in the natural hosts. Differences in the glycosylation profile between gastric human and animal mucins acting as glycan receptors for NHPH-associated adhesins, may be involved. The identification and characterization of the key molecules involved in the adhesion of gastric Helicobacter species to the gastric mucosa is important to understand the colonization and infection strategies displayed by different members of this genus.

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 Novel Functions for Glycosyltransferases Jhp0562 and GalT in Lewis Antigen Synthesis and Variation in Helicobacter pylori

2012 ◽  
Vol 80 (4) ◽  
pp. 1593-1605 ◽  
Author(s):  
Mary Ann Pohl ◽  
Sabine Kienesberger ◽  
Martin J. Blaser
Keyword(s):  
Helicobacter Pylori ◽  
Wild Type ◽  
Sequence Analyses ◽  
Upstream Gene ◽  
Content Type ◽  
Lewis Antigen ◽  
Mutant Strains ◽  
H Pylori

ABSTRACTLewis (Le) antigens are fucosylated oligosaccharides present in theHelicobacter pylorilipopolysaccharide. Expression of these antigens is believed to be important forH. pyloricolonization, since Le antigens also are expressed on the gastric epithelia in humans. A galactosyltransferase encoded by β-(1,3)galTis essential for production of type 1 (Leaand Leb) antigens. The upstream genejhp0562, which is present in many but not allH. pyloristrains, is homologous to β-(1,3)galTbut is of unknown function. BecauseH. pyloridemonstrates extensive intragenomic recombination, we hypothesized that these two genes could undergo DNA rearrangement. A PCR screen and subsequent sequence analyses revealed that the two genes can recombine at both the 5′ and 3′ ends. Chimeric β-(1,3)galT-like alleles can restore function in a β-(1,3)galTnull mutant, but neither native nor recombinantjhp0562can. Mutagenesis ofjhp0562revealed that it is essential for synthesis of both type 1 and type 2 Le antigens. Transcriptional analyses of both loci showed β-(1,3)galTexpression in all wild-type (WT) and mutant strains tested, whereasjhp0562was not expressed injhp0562null mutants, as expected. Sincejhp0562unexpectedly displayed functions in both type 1 and type 2 Le synthesis, we asked whethergalT, part of the type 2 synthesis pathway, had analogous functions in type 1 synthesis. Mutagenesis and complementation analysis confirmed thatgalTis essential for Lebproduction. In total, these results demonstrate thatgalTandjhp0562have functions that cross the expected Le synthesis pathways and thatjhp0562provides a substrate for intragenomic recombination to generate diverse Le synthesis enzymes.

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 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.

scholarly journals Tissue transglutaminase activity in human gastric mucosa according to Helicobacter pylori infection

2018 ◽  
Vol 243 (15-16) ◽  
pp. 1161-1164
Author(s):  
Maria Pina Dore ◽  
Giovanni Mario Pes ◽  
Alessandra Errigo ◽  
Alessandra Manca ◽  
Giuseppe Realdi
Keyword(s):  
Helicobacter Pylori ◽  
Animal Models ◽  
Gastric Mucosa ◽  
Natural History ◽  
Tissue Transglutaminase ◽  
Helicobacter Pylori Infection ◽  
Human Gastric Mucosa ◽  
Antral Mucosa ◽  
History Of ◽  
H Pylori

Tissue transglutaminase (t-TG) is a multifunctional protein involved in the healing of gastric erosions and ulcers in animal models. The aim of this study was to measure gastric t-TG activity in patients with dyspepsia according to Helicobacter pylori infection and cytotoxin-associated gene A (cagA) and vacuolating cytotoxin (vacA) subtype status. Patients undergoing upper endoscopy not taking any medications were enrolled. Tissue-TG activity was determined in homogenates of antral specimens using a radiometric assay and was expressed in pmol/mg. The cagA and vacA genotypes were determined by PCR amplification using gene-specific oligoprimers. Data from 46 patients were available (17 of them were positive for H. pylori). Antral t-TG activity was significantly increased in H. pylori positive patients compared to H. pylori negative patients (6437 ± 3691 vs. 3773 ± 1530 pmol/mg; P = 0.001) according to Mann–Whitney U test. Patients with H. pylori negative gastritis had higher t-TG activity than patients with normal gastric mucosa. The specimens infected with cagA positive strains (72%) displayed greater t-TG activity than cagA negative samples (7358 ± 4318 vs. 4895 ± 1062 pmol/mg; P = 0.237). Similarly, t-TG activity was higher in H. pylori vacA s1/m1 strains vs. vacA s1/m2 (7429 vs. 5045 pmol/mg; P = 0.744), and vacA s1/m1 vs. s2/m2 (7429 vs. 4489 pmol/mg; P = 0.651) but the results were not significant. No differences were found between histology, endoscopy features and t-TG activity. These results show that t-TG activity is significantly greater in gastritis associated with H. pylori infection, suggesting that this enzyme is induced by inflammation and may have an important role in the natural history of human gastritis. Impact statement Tissue transglutaminase (t-TG) is unique among TG enzymes because of its additional role in several physiological and pathological activities, including inflammation, fibrosis, and wound healing. The presence of t-TG has previously been described in the intestine of human and animal models, yet studies on t-TG activity in human gastric mucosa are missing. Helicobacter pylori infection is the major cause of gastritis and peptic ulcers. For the first time, our results show that t-TG activity was significantly higher in antral specimens of patients with chronic active gastritis associated with H. pylori infection compared to H. pylori negative chronic gastritis and normal antral mucosa. These findings suggest that t-TG has a role in the natural history of human gastritis, which requires further investigation but may be an avenue for new therapeutic options.

scholarly journals Variations in Helicobacter pylori Lipopolysaccharide To Evade the Innate Immune Component Surfactant Protein D

2005 ◽  
Vol 73 (11) ◽  
pp. 7677-7686 ◽  
Author(s):  
Wafa Khamri ◽  
Anthony P. Moran ◽  
Mulugeta L. Worku ◽  
Q. Najma Karim ◽  
Marjorie M. Walker ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Phase Variation ◽  
Surfactant Protein ◽  
Clinical Isolates ◽  
Surfactant Protein D ◽  
Human Gastric Mucosa ◽  
H Pylori

ABSTRACT Helicobacter pylori is a common and persistent human pathogen of the gastric mucosa. Surfactant protein D (SP-D), a component of innate immunity, is expressed in the human gastric mucosa and is capable of aggregating H. pylori. Wide variation in the SP-D binding affinity to H. pylori has been observed in clinical isolates and laboratory-adapted strains. The aim of this study was to reveal potential mechanisms responsible for evading SP-D binding and establishing persistent infection. An escape variant, J178V, was generated in vitro, and the lipopolysaccharide (LPS) structure of the variant was compared to that of the parental strain, J178. The genetic basis for structural variation was explored by sequencing LPS biosynthesis genes. SP-D binding to clinical isolates was demonstrated by fluorescence-activated cell sorter analyses. Here, we show that H. pylori evades SP-D binding through phase variation in lipopolysaccharide. This phenomenon is linked to changes in the fucosylation of the O chain, which was concomitant with slipped-strand mispairing in a poly(C) tract of the fucosyltransferase A (fucT1) gene. SP-D binding organisms are predominant in mucus in vivo (P = 0.02), suggesting that SP-D facilitates physical elimination. Phase variation to evade SP-D contributes to the persistence of this common gastric pathogen.

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