Influence of Lewis Antigen Expression by<i>Helicobacter pylori</i>on Bacterial Internalization by Gastric Epithelial Cells

Lozniewski, Alain; Haristoy, X.; Rasko, David A.; Hatier, R; Plénat, François; Taylor, Diane E.; Angioï-Duprez, K.

doi:10.1128/iai.71.5.2902-2906.2003

Cited by 32 publications

(18 citation statements)

References 29 publications

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“…Initially thought to mediate cell adhesion, current data indicate that Lewis antigens seem to have only a limited role in adhesion (386) and colonization (613). The finding that Lewis antigen expression enhances bacterial internalization by epithelial cells (374) suggests that Lewis antigen expression potentially affects the innate immune response. H. pylori LPS stimulates NF-B and IL-8 production in both epithelial cells and immune cells in a CagA-independent manner (53,359,384), but the NF-B activation observed in epithelial cells upon stimulation with H. pylori is not mediated by LPS (445).…”

Section: Role Of H Pylori Virulence Factorsmentioning

confidence: 99%

Pathogenesis ofHelicobacter pyloriInfection

2006

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SUMMARY Helicobacter pylori is the first formally recognized bacterial carcinogen and is one of the most successful human pathogens, as over half of the world's population is colonized with this gram-negative bacterium. Unless treated, colonization usually persists lifelong. H. pylori infection represents a key factor in the etiology of various gastrointestinal diseases, ranging from chronic active gastritis without clinical symptoms to peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Disease outcome is the result of the complex interplay between the host and the bacterium. Host immune gene polymorphisms and gastric acid secretion largely determine the bacterium's ability to colonize a specific gastric niche. Bacterial virulence factors such as the cytotoxin-associated gene pathogenicity island-encoded protein CagA and the vacuolating cytotoxin VacA aid in this colonization of the gastric mucosa and subsequently seem to modulate the host's immune system. This review focuses on the microbiological, clinical, immunological, and biochemical aspects of the pathogenesis of H. pylori.

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Section: Role Of H Pylori Virulence Factorsmentioning

confidence: 99%

Pathogenesis ofHelicobacter pyloriInfection

2006

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“…H. pylori fucosyltransferases (FucTs) are responsible for the last steps in the biosynthesis of Lewis antigens. The molecular mimicry of host cell surface antigens has been suggested to mask the pathogen from host immune surveillance and thus plays an important role in colonization and long term infection in the stomach (10). Furthermore, H. pylori continuously alters the expression of Lewis antigens, a process known as phase variation, to generate several LPS variants in one bacterial population and to display structural heterogeneity.…”

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Structure and Mechanism of Helicobacter pylori Fucosyltransferase

Sun

Lin

et al. 2007

Journal of Biological Chemistry

118

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Helicobacter pylori ␣1,3-fucosyltransferase (FucT) is involved in catalysis to produce the Lewis x trisaccharide, the major component of the bacteria's lipopolysaccharides, which has been suggested to mimic the surface sugars in gastric epithelium to escape host immune surveillance. We report here three x-ray crystal structures of FucT, including the FucT⅐GDP-fucose and FucT⅐GDP complexes. The protein structure is typical of the glycosyltransferase-B family despite little sequence homology. We identified a number of catalytically important residues, including Glu-95, which serves as the general base, and Glu-249, which stabilizes the developing oxonium ion during catalysis. The residues Arg-195, Tyr-246, Glu-249, and Lys-250 serve to interact with the donor substrate, GDP-fucose. Variations in the protein and ligand conformations, as well as a possible FucT dimer, were also observed. We propose a catalytic mechanism and a model of polysaccharide binding not only to explain the observed variations in H. pylori lipopolysaccharides, but also to facilitate the development of potent inhibitors.

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“…Stock solutions were prepared in acetonitrile, and further dilutions were made in sterile water. H. pylori strain 26695, which was previously adapted for use in the gastric xenograft model (23), was used for graft inoculation. The strain was grown on Columbia agar supplemented with 10% horse blood under microaerobic conditions as previously described (22).…”

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confidence: 99%

“…Mucus was sampled for qualitative culture onto blood agar, and three biopsies were taken from antrum-adjacent sites for quantitative culture and histology. The levels of colonization and the concentrations of intracellular bacteria were determined by quantitative culture as previously described (23). For histological studies, specimens were processed by standard methods and stained with hematoxylineosin to assess the intensity of gastritis and with a modified Giemsa stain for detection of H. pylori (22).…”

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confidence: 99%

Efficacyof Sulforaphane in EradicatingHelicobacter pyloriin HumanGastric Xenografts Implanted in NudeMice

Haristoy

Angioï-Duprez²,

Duprez

et al. 2003

Antimicrob Agents Chemother

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Sulforaphane, an isothiocyanate abundant in the form of its glucosinolate precursor in broccoli sprouts, has shown in vitro activity against Helicobacter pylori. We evaluated the effect of sulforaphane in vivo against this bacterium by using human gastric xenografts in nude mice. H. pylori was completely eradicated in 8 of the 11 sulforaphane-treated grafts. This result suggests that sulforaphane might be beneficial in the treatment of H. pylori-infected individuals.The recommended treatment of Helicobacter pylori-associated diseases today includes a combination of two or more antibiotics with an inhibitor of acid secretion. However, even with these treatments, some bacteria may persist, in a nongrowing, tolerant form or possibly intracellularly (5,7,10). This may lead to eradication failure, which is defined as the persistence of H. pylori at least 1 month after the end of antimicrobial therapy (9). Moreover, development of resistance of H. pylori strains to one or more of the antibiotics commonly used has been demonstrated previously (28). Thus, a need for new therapeutic agents that are effective against extracellular and potentially intracellular forms of H. pylori exists. We recently showed that sulforaphane, an isothiocyanate abundant in the form of its glucosinolate precursor in broccoli and broccoli sprouts, is a potent bactericidal agent against both extra-and intracellular H. pylori in vitro (11). Substantial quantities of isothiocyanates (up to 100 mg daily) and even greater quantities of their glucosinolate precursors are widely consumed by humans (12,13,29). They may act locally within the gastrointestinal tract or may distribute systemically after conversion to their cognate isothiocyanates (12,15,34). In this study, we investigated the efficacy of sulforaphane in vivo against H. pylori by using a recently developed model which uses human gastric xenografts in nude mice (22).Sulforaphane, i.e., [(Ϫ)-1-isothiocyanato-(4R)-(methylsulfinyl)butane] was kindly provided by J. W. Fahey (Johns Hopkins University School of Medicine, Baltimore, Md.). Stock solutions were prepared in acetonitrile, and further dilutions were made in sterile water. H. pylori strain 26695, which was previously adapted for use in the gastric xenograft model (23), was used for graft inoculation. The strain was grown on Columbia agar supplemented with 10% horse blood under microaerobic conditions as previously described (22). For this isolate, the MIC of sulforaphane was 4 g/ml, as determined by using the agar dilution method (pH 7.4) as recommended by the National Committee for Clinical Laboratory Standard (NCCLS) (30).Xenografts exhibiting human mature gastric epithelium and acidic secretion were obtained in nude mice as previously described (22) and with the approval of the French National Consultative Ethical Committee. Bacterial inoculation was performed by using a catheter that was implanted in the xenograft lumen (22). Two weeks after inoculation, each graft was microsurgically opened. Mucus was sampled for qualitative cult...

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Influence of Lewis Antigen Expression byHelicobacter pylorion Bacterial Internalization by Gastric Epithelial Cells

Abstract: The role of Helicobacter pylori lipopolysaccharide (LPS) Lewis antigens in infection is

Cited by 32 publications

References 29 publications

Pathogenesis ofHelicobacter pyloriInfection

Pathogenesis ofHelicobacter pyloriInfection

Structure and Mechanism of Helicobacter pylori Fucosyltransferase

Efficacyof Sulforaphane in EradicatingHelicobacter pyloriin HumanGastric Xenografts Implanted in NudeMice

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