| 1. |
- Aspholm-Hurtig, Marina, et al.
(författare)
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Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin.
- 2004
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 305:5683, s. 519-22
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Tidskriftsartikel (refereegranskat)abstract
- Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations.
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| 2. |
- Hynes, Sean, et al.
(författare)
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Glycoconjugate Binding of Gastric and Enterohepatic Helicobacter spp.
- 2003
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Ingår i: Infection and Immunity. - 1098-5522. ; 71:5, s. 2976-2980
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori is able to utilize several lectin-like, protein-carbohydrate interactions for binding to mucins, cell surfaces, and extracellular matrix proteins. As determined by hemagglutination assays and binding of radiolabeled bacteria to glycosphingolipids on thin-layer chromatograms, strains of gastric helicobacters and enterohepatic helicobacters, including Helicobacter canis, Helicobacter hepaticus, and Helicobacter bilis, also demonstrated evidence for the presence of lectin-hemagglutinin adhesins. In addition, in H. hepaticus and H. bilis, binding may be sialic acid dependent. The presence or absence and differences in the levels of activity of lectin adhesins may reflect the species' ecological niche.
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| 3. |
- Mahdavi, Jafar, et al.
(författare)
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Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation
- 2002
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Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 297:5581, s. 573-578
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori adherence in the human gastric mucosa involves specific bacterial adhesins and cognate host receptors. Here, we identify sialyl-dimeric-Lewis x glycosphingolipid as a receptor for H. pylori and show that H. pylori infection induced formation of sialyl-Lewis x antigens in gastric epithelium in humans and in a Rhesus monkey. The corresponding sialic acid-binding adhesin (SabA) was isolated with the "retagging" method, and the underlying sabA gene (JHP662/HP0725) was identified. The ability of many H. pylori strains to adhere to sialylated glycoconjugates expressed during chronic inflammation might thus contribute to virulence and the extraordinary chronicity of H. pylori infection.
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| 4. |
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| 5. |
- Roche, Niamh, 1969
(författare)
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Glycosphingolipid interactions of Helicobacter pylori and F1C-fimbriated Escherichia coli
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to investigate glycosphingolipid interactions of the human pathogens Helicobacter pylori and F1C-fimbriated uropathogenic Escherichia coli. Of particular interest were interactions of H. pylori to complex gangliosides, the role played by H. pylori neutrophil activating protein (HP-NAP) and the SabA adhesin in the binding of H. pylori to complex gangliosides, and the factors influencing binding of H. pylori to such structures. Additionally, the interaction between F1C-fimbriated E. coli and glycosphingolipids from its target tissue was investigated. Glycosphingolipids were isolated from different sources and characterised using mass spectrometry, proton NMR, enzyme degradation and by the binding of relevant antibodies and lectins. Isolated glycosphingolipids were separated by TLC and binding by 35S-labelled bacteria was investigated by means of the chromatogram-binding assay. Binding by H. pylori to the complex gangliosides sialyl-neolactohexaosylceramide and sialyl-neolactooctaosylceramide isolated from human gastric adenocarcinoma and sialyl-dimeric-Lex from human gall bladder adenocarcinoma was obtained. To investigate the factors influencing the binding of H. pylori to complex gangliosides and the involvement of HP-NAP and the SabA adhesin a ganglioside bank was generated, against which the binding of H. pylori was tested. Binding to complex gangliosides was eliminated in a SabA knockout mutant but not in a HP-NAP knockout mutant. Binding by H. pylori to serial dilutions of linear, fucosylated and branched structures revealed that chain length, fucosylation and branching influence binding. Binding by F1C-fimbriated uropathogenic E. coli to the monoglycosylceramide region of rat, canine and human kidney with additional binding in the tri-tetraglycosylceramide regions of canine and human kidney was obtained. Structural analysis revealed the mono- and triglycosylceramide binding-active components to be Galb1Cer and Gala4Galb4Glcb1Cer with phytosphingosine and hydroxy fatty acids. The results obtained of this study show that H. pylori interacts with complex gangliosides, that this interaction is mediated solely by the SabA adhesin but not HP-NAP. Factors influencing binding were identified as increasing chain length, fucosylation and the degree of sialylation of branches. Two binding-active non-acid glycosphingolipids from human and canine kidney were characterised as Galb1Cer and Gala4Galb4Glcb1Cer with binding of E. coli requiring phytosphingosine and hydroxy fatty acid.
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| 6. |
- Roche, Niamh, 1969, et al.
(författare)
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Helicobacter pylori and complex gangliosides.
- 2004
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Ingår i: Infection and immunity. - 0019-9567. ; 72:3, s. 1519-29
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Tidskriftsartikel (refereegranskat)abstract
- Recognition of sialic acid-containing glycoconjugates by the human gastric pathogen Helicobacter pylori has been repeatedly demonstrated. To investigate the structural requirements for H. pylori binding to complex gangliosides, a large number of gangliosides were isolated and characterized by mass spectrometry and proton nuclear magnetic resonance. Ganglioside binding of sialic acid-recognizing H. pylori strains (strains J99 and CCUG 17874) and knockout mutant strains with the sialic acid binding adhesin SabA or the NeuAcalpha3Galbeta4GlcNAcbeta3Galbeta4GlcNAcbeta-binding neutrophil-activating protein HPNAP deleted was investigated using the thin-layer chromatogram binding assay. The wild-type bacteria bound to N-acetyllactosamine-based gangliosides with terminal alpha3-linked NeuAc, while gangliosides with terminal NeuGcalpha3, NeuAcalpha6, or NeuAcalpha8NeuAcalpha3 were not recognized. The factors affecting binding affinity were identified as (i) the length of the N-acetyllactosamine carbohydrate chain, (ii) the branches of the carbohydrate chain, and (iii) fucose substitution of the N-acetyllactosamine core chain. While the J99/NAP(-) mutant strain displayed a ganglioside binding pattern identical to that of the parent J99 wild-type strain, no ganglioside binding was obtained with the J99/SabA(-) mutant strain, demonstrating that the SabA adhesin is the sole factor responsible for the binding of H. pylori bacterial cells to gangliosides.
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| 7. |
- Roche, Niamh, 1969, et al.
(författare)
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Human gastric glycosphingolipids recognized by Helicobacter pylori vacuolating cytotoxin VacA.
- 2007
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Ingår i: Microbes and infection / Institut Pasteur. - : Elsevier BV. - 1286-4579. ; 9:5, s. 605-14
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Tidskriftsartikel (refereegranskat)abstract
- Many bacterial toxins utilize cell surface glycoconjugate receptors for attachment to target cells. In the present study the potential carbohydrate binding of Helicobacter pylori vacuolating cytotoxin VacA was investigated by binding to human gastric glycosphingolipids on thin-layer chromatograms. Thereby a distinct binding of the toxin to two compounds in the non-acid glycosphingolipid fraction was detected. The VacA-binding glycosphingolipids were isolated and characterized by mass spectrometry and proton NMR as galactosylceramide (Galbeta1Cer) and galabiosylceramide (Galalpha4Galbeta1Cer). Comparison of the binding preferences of the protein to reference glycosphingolipids from other sources showed an additional recognition of glucosylceramide (Glcbeta1Cer), lactosylceramide (Galbeta4Glcbeta1Cer) and globotriaosylceramide (Galalpha4Galbeta4Glcbeta1Cer). No binding to the glycosphingolipids recognized by the VacA holotoxin was obtained with a mutant toxin with deletion of the 37 kDa fragment of VacA (P58 molecule). Collectively our data show that the VacA cytotoxin is a glycosphingolipid binding protein, where the 37 kDa moiety is required for carbohydrate recognition. The ability to bind to short chain glycosphingolipids will position the toxin close to the cell membrane, which may facilitate toxin internalization.
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