scholarly journals Rhesus monkey gastric mucins: oligomeric structure, glycoforms and Helicobacter pylori binding1

2004 ◽  
Vol 379 (3) ◽  
pp. 765-775 ◽  
Author(s):  
Sara LINDÉN ◽  
Thomas BORÉN ◽  
André DUBOIS ◽  
Ingemar CARLSTEDT

Mucins isolated from the stomach of Rhesus monkey are oligomeric glycoproteins with a similar mass, density, glycoform profile and tissue localization as human MUC5AC and MUC6. Antibodies raised against the human mucins recognize those from monkey, which thus appear to be orthologous to those from human beings. Rhesus monkey muc5ac and muc6 are produced by the gastric-surface epithelium and glands respectively, and occur as three distinct glycoforms. The mucins are substituted with the histo blood-group antigens B, Lea (Lewis a), Leb, Lex, Ley, H-type-2, the Tn-antigen, the T-antigen, the sialyl-Lex and sialyl-Lea structures, and the expression of these determinants varies between individuals. At neutral pH, Helicobacter pylori strains expressing BabA (blood-group antigen-binding adhesin) bind Rhesus monkey gastric mucins via the Leb or H-type-1 structures, apparently on muc5ac, as well as on a smaller putative mucin, and binding is inhibited by Leb or H-type-1 conjugates. A SabA (sialic acid-binding adhesin)-positive H. pylori mutant binds to sialyl-Lex-positive mucins to a smaller extent compared with the BabA-positive strains. At acidic pH, the microbe binds to mucins substituted by sialylated structures such as sialyl-Lex and sialylated type-2 core, and this binding is inhibited by DNA and dextran sulphate. Thus mucin–H. pylori binding occurs via at least three different mechanisms: (1) BabA-dependent binding to Leb and related structures, (2) SabA-dependent binding to sialyl-Lex and (3) binding through a charge-mediated mechanism to sialylated structures at low pH values.

2008 ◽  
Vol 57 (5) ◽  
pp. 585-591 ◽  
Author(s):  
Eleonora Altman ◽  
Heriberto Fernández ◽  
Vandana Chandan ◽  
Blair A. Harrison ◽  
Myra Wilson Schuster ◽  
...  

Previous studies have shown that the LPS of Helicobacter pylori isolated from North American and European hosts predominantly expresses type 2 Lewis x (Lex) and Ley epitopes, whilst the LPS from Asian strains has the capacity to express type 1 Lea and Leb structures. The aim of this study was to evaluate the expression of Le antigens and the cytotoxin-associated antigen (CagA) by H. pylori isolates from Chile. A total of 38 isolates were screened. The expression of Le antigens and CagA was determined by whole-cell indirect ELISA, using commercially available monoclonal anti-Le and polyclonal anti-CagA antibodies. LPS profiles of H. pylori isolates were assessed by gel electrophoresis and Western blotting. Expression of Lex and/or Ley epitopes was confirmed in 32/38 isolates (84 %), whilst 9/38 isolates (24 %) expressed type 1 Leb blood group determinants, in addition to type 2 Lex and Ley structures. Six strains (16 %) were non-typeable. The majority of H. pylori strains examined were CagA-positive (83.3 %).


2012 ◽  
Vol 80 (4) ◽  
pp. 1593-1605 ◽  
Author(s):  
Mary Ann Pohl ◽  
Sabine Kienesberger ◽  
Martin J. Blaser

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.


2018 ◽  
Vol 293 (44) ◽  
pp. 17248-17266 ◽  
Author(s):  
Chunsheng Jin ◽  
Angela Barone ◽  
Thomas Borén ◽  
Susann Teneberg

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.


2005 ◽  
Vol 83 (5) ◽  
pp. 589-596 ◽  
Author(s):  
Eleonora Altman ◽  
Blair A Harrison ◽  
Tomoko Hirama ◽  
Vandana Chandan ◽  
Rebecca To ◽  
...  

The cell envelope of Helicobacter pylori contains lipopolysaccharide (LPS), the O-chain of which expresses type 2 Lexand Leyblood group antigens, which mimic human gastric mucosal cell-surface glycoconjugates and may contribute to the survival of H. pylori in gastric mucosa. Here we describe the generation of monoclonal antibodies specific for Lexand Leyblood group determinants and the characterization of their binding properties using purified, structurally defined H. pylori LPS, synthetic glycoconjugates, and H. pylori cells. Analysis of oligosaccharide binding by SPR provided a rapid and reliable means for characterization of antibody affinities. One of the antibodies, anti-Lex, was of IgG3 subclass and had superior binding characteristics as compared with the commercially available anti-LexIgM. These antibodies could have potential in the immunodiagnosis of certain types of cancer, in serotyping of H. pylori isolates, and in structure–function studies.Key words: Helicobacter pylori, lipopolysaccharide, monoclonal antibodies, Lewis determinants, immunodiagnosis.


Glycobiology ◽  
2000 ◽  
Vol 10 (7) ◽  
pp. 701-713 ◽  
Author(s):  
M. A. Monteiro ◽  
P.-y. Zheng ◽  
B. Ho ◽  
S.-i. Yokota ◽  
K.-i. Amano ◽  
...  

2000 ◽  
Vol 68 (2) ◽  
pp. 937-941 ◽  
Author(s):  
Michael A. Heneghan ◽  
Ciaran F. McCarthy ◽  
Anthony P. Moran

ABSTRACT As Lewis a (Lea) and Lewis b (Leb) blood group antigens are isoforms of Lewis x (Lex) and Lewis y (Ley) and are expressed in the gastric mucosa, we evaluated whether the patterns of expression of Lex and Ley on Helicobacter pylorilipopolysaccharides reflected those of host expression of Lea and Leb. When 79 patients (secretors and nonsecretors) were examined for concordance between bacterial and host Le expression, no association was found (χ2 = 5.734, 3 df, P = 0.125), nor was there a significant difference between the amount of Lex or Ley expressed on isolates from ulcer and chronic gastritis patients (P > 0.05). Also, the effect of host and bacterial expression of Le antigens on bacterial colonization and the observed inflammatory response was assessed. In ulcer patients, Lex expression was significantly related to neutrophil infiltration (r s = 0.481,P = 0.024), whereas in chronic gastritis patients significant relationships were found between Lexexpression and H. pylori colonization density (r s = 0.296, P = 0.03), neutrophil infiltrate (r s = 0.409,P = 0.001), and lymphocyte infiltrate (r s = 0.389, P = 0.002). Furthermore, bacterial Ley expression was related to neutrophil (r s = 0.271, P= 0.033) and lymphocyte (r s = 0.277,P = 0.029) infiltrates. Thus, although no evidence of concordance was found between bacterial and host expression of Le determinants, these antigens may be crucial for bacterial colonization, and the ensuing inflammatory response appears, at least in part, to be influenced by Le antigens.


Author(s):  
Chaima Jemai ◽  
Rim Rachdi ◽  
Sonia Bellamine ◽  
Lamia Bouallegue ◽  
Faika Ben Mami

Introduction: The association between diabetes and Helicobacter Pylori (H. Pylori) infection remains controversial in the literature. The aim of our study was to search an association between diabetes and H. Pylori infection. Methods: This is a case-control study carried out in 2017 over 3 months (September-October-November), collecting 120 patients with dyspepsia, matched for age and gender into two groups: a group of 77 patients with diabetes, and a group of control cases made of 43 non-diabetics. Diabetes was defined according to the American Diabetes Association (ADA) of 2017. Clinical, biological, endoscopic and anatomopathological data were collected from medical records. Results: The average age of the patients was 50±2,1 year. The sex ratio was 0.51. 34.2% (n=41) patients were male. Diabetes was type 2 in the majority of cases (88.31%) and type 1 in 11.68% only. H. Pylori infection was more prevalent in diabetics (19.48%, 11.63%, p=0.27). H. Pylori infection was more prevalent in type 1 diabetics (44.44%, 16.18%, p= 0.04). The frequency of upper endoscopic lesions in diabetics and controls was 70.13% and 74.42%, respectively. Chronic gastritis, gastric atrophy, and intestinal metaplasia were found in 61%, 3.9% and 2.6% of the cases in the group of diabetics and 62.79%, 6.98% and 4.65% respectively in the control group (p= not significant (NS)). Conclusion: Our study shows the absence of a significant association between diabetes and H. Pylori infection, as well as the absence of endoscopic and histological specificities of this infection in patients with diabetes.


2021 ◽  
Vol 49 (12) ◽  
pp. 030006052110588
Author(s):  
Azar Dokht Khosravi ◽  
Mehrandokht Sirous ◽  
Morteza Saki ◽  
Sakineh Seyed-Mohammadi ◽  
Seyed Reza Modares Mousavi ◽  
...  

Objective To investigate correlations between ABO/rhesus (Rh) blood group antigens and anti- Helicobacter pylori and anti-cytotoxin-associated gene A (CagA) seropositivity in blood donors. Methods A total of 311 blood donors were enrolled. ABO and Rh blood groups were determined using hemagglutination tests. Specific anti- H. pylori IgG and anti-CagA IgG antibodies in sera were quantitated by enzyme-linked immunosorbent assay. Correlations between blood groups and anti- H. pylori and anti-CagA seropositivity were evaluated using the Chi-square test. Results O+ was the most frequent blood type (38%, n = 118). Anti- H. pylori IgG seropositivity was observed in 240 (77.2%) blood donors, while anti-CagA IgG seropositivity was observed in 132 (42.5%) blood donors. Although seropositivity rates for both anti- H. pylori and anti-CagA IgG were higher in individuals with blood type O, no statistically significant associations were observed between seropositivity and any ABO/Rh blood groups. Conclusion Individuals with blood type O may have higher rates of H. pylori seropositivity.


2001 ◽  
Vol 79 (4) ◽  
pp. 449-459 ◽  
Author(s):  
Mario A Monteiro ◽  
Frank St Michael ◽  
David A Rasko ◽  
Diane E Taylor ◽  
J Wayne Conlan ◽  
...  

Helicobacter pylori is a widespread Gram-negative bacterium responsible for the onset of various gastric pathologies and cancers in humans. A familiar trait of H. pylori is the production of cell-surface lipopolysaccharides (LPSs; O-chain [Formula: see text] core [Formula: see text] lipid A) with O-chain structures analogous to some mammalian histo-blood-group antigens, those being the Lewis determinants (Lea, Leb, Lex, sialyl Lex, Ley) and blood groups A and linear B. Some of these LPS antigens have been implicated as autoimmune, adhesion, and colonization components of H. pylori pathogenic mechanisms. This article describes the chemical structures of LPSs from H. pylori isolated from subjects with no overt signs of disease. Experimental data from chemical- and spectroscopic-based studies unanimously showed that these H. pylori manufactured extended heptoglycans composed of 2- and 3-linked D-glycero-α-D-manno-heptopyranose units and did not express any blood-group O-antigen chains. The fact that another H. pylori isolate with a similar LPS structure was shown to be capable of colonizing mice indicates that H. pylori histo-blood-group structures are not an absolute prerequisite for colonization in the murine model also. The absence of O-chains with histo-blood groups may cause H. pylori to become inept in exciting an immune response. Additionally, the presence of elongated heptoglycans may impede exposure of disease-causing outer-membrane antigens. These factors may render such H. pylori incapable of creating exogenous contacts essential for pathogenesis of severe gastroduodenal diseases and suggest that histo-blood groups in the LPS may indeed play a role in inducing a more severe H. pylori pathology.Key words: lipopolysaccharide, carbohydrates, glycobiology, Helicobacter pylori, histo-blood groups.


2021 ◽  
Vol 16 (8) ◽  
Author(s):  
Thai Doan Ky ◽  
Hoang Kim Ngan ◽  
Pham Minh Ngoc Quang ◽  
Luu Tuan Thanh

Mục tiêu: Đánh giá giá trị của nội soi dải tần hẹp (NBI) trong chẩn đoán nhiễm Helicobacter pylori (H. pylori). Đối tượng và phương pháp: Mô tả cắt ngang, hình ảnh nội soi NBI được phân loại thành 4 type dựa trên cấu trúc khe tuyến và mạch máu dưới biểu mô. Bệnh nhân đượclàm urease test và mô bệnh học để đối chiếu, qua đó đánh giá giá trị của nội soi NBI. Kết quả: 89 bệnh nhân được đưa vào nghiên cứu từ ngày 01/11/2020 đến ngày 30/05/2021, trong đó 32 bệnh nhân được xếp loại type 1 chiếm 36%, 34 bệnh nhân xếp loại type 2 (38,2%), 21 bệnh nhân xếp loại type 3 (23,6%) và 2 bệnh nhân được xếp loại type 4 (2,2%), 36 bệnh chẩn đoán dương tính chiếm 53,7%, 31 bệnh nhân âm tính chiếm 46,3%. Độ nhạy của type 2 + type 3 + type 4 trong chẩn đoán H. pylori là 97,22%, độ đặc hiệu là 77,42%, giá trị dự báo dương tính là 83,33%, giá trị dự báo âm tính là 96%. Kết luận: Nội soi NBI có giá trị cao trong chẩn đoán nhiễm H. pylori.


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