Molecular Structure, Biosynthesis, and Pathogenic Roles of Lipopolysaccharides

Anthony P. Moran

doi:10.1128/9781555818005.ch8

Chapter 8 : Molecular Structure, Biosynthesis, and Pathogenic Roles of Lipopolysaccharides

Author: Anthony P. Moran¹

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Affiliations: 1: Department of Microbiology, National University of Ireland, Galway, Ireland

Content Type: Monograph

Publication Year: 2001

Category: Bacterial Pathogenesis

Book DOI: 10.1128/9781555818005

Chapter DOI: 10.1128/9781555818005.ch8

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Abstract:

This chapter reviews the attributes and structure of Helicobacter pylori lipopolysaccharides (LPSs), especially the relationship between molecular structure and pathogenesis. The outermost O-specific polysaccharide chain is a polymer of identical repeating units that may contain up to seven different sugars, depending on the bacterial species and strain. Fresh clinical isolates of H. pylori produce highmolecular-weight, smooth-form LPS (S-LPS). Compared with other bacterial species, the core regions of H. pylori strains exhibit an unusual conformation as determined by chemical structural studies. As exemplified by the core oligosaccharide of H. pylori NCTC 11637, a branching occurs from the D-glycero-D-manno-heptose (DD-Hep) residue in the inner core through a second such residue to which the first repeating unit of the O-polysaccharide chain is attached. Survival of H. pylori below pH 4 is dependent on urease activity, whereas urease-independent mechanisms, although less well characterized, operate at greater than pH 4. Bacterial interactions with extracellular and basement membrane proteins play an important role in the pathogenesis and virulence of a number of infections. Elevated pepsinogen, a precursor of mucolytic and barrier-breaking pepsin, is considered a marker for the development and recurrence of duodenal ulcers.

Citation: Moran A. 2001. Molecular Structure, Biosynthesis, and Pathogenic Roles of Lipopolysaccharides, p 81-95. In Mobley H, Mendz G, Hazell S (ed), Helicobacter pylori. ASM Press, Washington, DC. doi: 10.1128/9781555818005.ch8

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Molecular Structure, Biosynthesis, and Pathogenic Roles of Lipopolysaccharides

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Figure 1

Schematic representation of the three major domains of the LPS molecule.

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Figure 1

Schematic representation of the three major domains of the LPS molecule.

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Figure 3

Proposed chemical structure of the polysaccharide moiety of LPS of H. pylori NCTTC 11637 ( 10 ). Further substitution of the lateral DD-Hep (indicated by arrow) by heptose and glucose occurs in some other H. pylori strains. Abbreviations: Fuc, fucose; Gal, galactose; Glc, glucose; GlcNAc, N-acetylglucosamine; DD-Hep, D-glycero-D-manno-heptose; LD-Hep, L-glycero-D-manno-heptose; Kdo, 3-deoxy-D-manno-2-octulosonic acid.

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Figure 3

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Figure 4

Structural relationship between A, B, H, and Lewis (Le) blood group determinants. Except for fucose, which is in the L-form, all sugars possess the D-configuration. Abbreviations: Fuc, fucose; Gal, galactose; GalNAc, N-acetylgalactosamine; Glc, glucose; GlcNAc, N-acetylglucosamine; NANA, N-acetylneuraminic (sialic) acid.

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Figure 4

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Figure 5

Modular structures of the polysaccharide component of some examples of H. pylori LPS. For an explanation of sugar abbreviations, see the legend to Fig. 3 .

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Figure 5

Modular structures of the polysaccharide component of some examples of H. pylori LPS. For an explanation of sugar abbreviations, see the legend to Fig. 3 .

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Figure 2

Proposed chemical structures of (A) the predominant lipid A molecular structure found in H. pylori R-LPS and S-LPS and (B) a minor lipid A species found in H. pylori S-LPS ( 71 ). Numbers in circles refer to the number of carbon atoms in acyl chains. Further heterogeneity occurs by nonstoichiometric replacement of 3-(18:0)-O-18:0 with 3-(16:0)-O-18:0 on the nonreducing glucosamine unit of the lipid A backbone. Polar headgroups are indicated by R' (phosphate or ethanolamine) and R" (H or phosphate).

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Figure 2

References

/content/book/10.1128/9781555818005.chap8

1. Aim, R. A.,, L.-S. L. Ling,, D. T. Moir,, B. L. King,, E. D. Brown,, P. C. Doig,, D. R. Smith,, B. Noonan,, B. C. Guild,, B. L. de Jonge,, G. Carmel,, P. J. Tummino,, A. Caruso,, M. Uria-Nickelsen,, D. M. Mills,, C. Ives,, R. Gibson,, D. Merberg,, S. D. Mills,, Q. Jiang,, D. E. Taylor,, G. F. Vovis,, and T. J. Trust. 1999. Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature 397: 176– 180.

2. Appelmelk, B. J.,, G. Faller,, D. Claeys,, T. Kirchner,, and C. M.J. E. Vandenbroucke-Grauls. 1998. Bugs on trial: the case of Helicobacter pylori and autoimmunity. Immunol. Today 19: 296– 299.

3. Appelmelk, B. J.,, S. L. Martin,, M. A. Monteiro,, C. A. Clayton,, A. A. McColm,, P. Zheng,, T. Verboom,, J. J. Maaskant,, D. H. van den Eijnden,, C. H. Hokke,, M. B. Perry,, C. M. J. E. Vandenbroucke-Grauls,, and J. G. Kusters. 1999. Phase variation in Helicobacter pylori lipopolysaccharide due to changes in the lengths of poly(C) tracts in α3-fucosyltransferase genes. Infect. Immun. 67: 5361– 5366.

4. Appelmelk, B. J.,, R. Negrini,, A. P. Moran,, and E. J. Kuipers. 1997. Molecular mimicry between Helicobacter pylori and the host. Trends Microbiol. 5: 70– 73.

5. Appelmelk, B. J.,, B. Shiberu,, C. Trinks,, N. Tapsi,, P. Y. Zheng,, T. Verboom,, J. Maaskant,, C. H. Hokke,, W. E. C. M. Schiphorst,, D. Blanchard,, I. M. Simoons-Smit,, D. H. van den Eijnden,, and C. M. J. E. Vandenbroucke-Grauls. 1998. Phase variation in Helicobacter pylori lipopolysaccharide. Infect. Immun. 66: 70– 76.

6. Appelmelk, B. J.,, I. M. Simoons-Smit,, R. Negrini,, A. P. Moran,, G. O. Aspinall,, J. G. Forte,, T. de Vries,, H. Quan,, T. Verboom,, J. J. Maaskant,, P. Ghiara,, E. J. Kuipers,, E. Bloemena,, T. M. Tadema,, R. R. Townsend,, K. Tyagarajan,, J. M. Crothers,, M. A. Monteiro,, A. Savio,, and J. de Graaf. 1996. Potential role of molecular mimicry between Helicobacter pylori lipopolysaccharide and host Lewis blood group antigens in autoimmunity. Infect. Immun. 64: 2031– 2040.

7. Aspinall, G. O.,, A. S. Mainkar,, and A. P. Moran. 1999. A structural comparison of lipopolysaccharides from two strains of Helicobacter pylori, of which one strain (442) does and the other strain (471) does not stimulate pepsinogen secretion. Glycobiology 9: 1235– 1245.

8. Aspinall, G. O.,, and M. A. Monteiro. 1996. Lipopolysaccharides of Helicobacter pylori strains P466 and M019: structures of the O antigen and core oligosaccharide regions. Biochemistry 35: 2498– 2504.

9. Aspinall, G. O.,, M. A. Monteiro,, H. Pang,, E. J. Walsh,, and A. P. Moran. 1994. O antigen chains in the lipopolysaccharide of Helicobacter pylori NCTC 11637. Carbohydr. Lett. 1: 151– 156.

10. Aspinall, G. O.,, M. A. Monteiro,, H. Pang,, E. J. Walsh,, and A. P. Moran. 1996. Lipopolysaccharide of the Helicobacter pylori type strain NCTC 11637 (ATCC 43504): structure of the O antigen chain and core oligosaccharide regions. Biochemistry 35: 2489– 2497.

11. Aspinall, G. O.,, M. A. Monteiro,, R. T. Shaver,, L. A. Kurjanc-zyk,, and J. L. Penner. 1997. Lipopolysaccharides of Helicobacter pylori serogroups 0:3 and 0:6. Structures of a class of lipopolysaccharides with reference to the location of oligomeric units of D-glycero-a-D-manno-heptose residues. Eur. J. Biochem. 248: 592– 601.

12. Aspinall, G. O.,, and A. P. Moran,. 1997. Helicobacter pylori lipopolysaccharide structure and mimicry of Lewis blood group antigens, p. 34– 42. In A. P. Moran, and C. A. O'Morain (ed.), Pathogenesis and Host Response in Helicobacter pylori Infections. Normed Verlag, Bad Homburg, Germany.

13. Baker, P. J.,, T. Hraba,, C. E. Taylor,, P. W. Stashak,, M. B. Fauntieroy,, U. Zähringer,, K. Takayama,, T. R. Sievert,, X. Hronowski,, R.J. Cotter,, and G. Perez-Perez. 1994. Molecular structures that influence the immunomodulatory properties of the lipid A and inner core region oligosaccharides of bacterial lipopolysaccharides. Infect. Immun. 62: 2269– 2257.

14. Berg, D. E.,, P. S. Hoffman,, B.J. Appelmelk,, and J. G. Küsters. 1997. The Helicobacter pylori genome sequence: genetic factors for long life in the gastric mucosa. Trends Microbiol. 5: 468– 474.

15. Birkholz, S.,, U. Knipp,, C. Nietzki,, R. J. Adamek,, and W. Opferkuch. 1993. Immunological activity of lipopolysaccharide of Helicobacter pylori on human peripheral mononuclear blood cells in comparison to lipopolysaccharides of other intestinal bacteria. FEMS Immunol. Med. Microbiol. 6: 317– 324.

16. Bukholm, G.,, T. Tannaes,, P. Nedenskov,, Y. Esbensen,, H. J. Grav,, T. Hovig,, S. Ariansen,, and I. Guldvog. 1997. Colony variation of Helicobacter pylori: pathogenic potential is correlated to cell wall lipid composition. Scand. J. Gastroenterol. 32: 445– 454.

17. Campbell, B. J.,, K. A. Rogerson,, and J. M. Rhodes. 1999. Adherence of Helicobacter pylori to human gastric epithelium mediated by an epithelial cell-surface Lewis" carbohydrate-binding protein. Gastroenterology 116: A131.

18. Cave, T. R.,, and D. R. Cave. 1991. Helicobacter pylori stimulates pepsin secretion from isolated rabbit gastric glands. Scand. J. Gastroenterol. (Suppl. 181) 26: 9– 14.

19. Claeys, D.,, G. Faller,, B. J. Appelmelk,, R. Negrini,, and T. Kirchner. 1998. The gastric H +,K +-ATPase is a major autoantigen in chronic Helicobacter pylori gastritis with body mucosa atrophy. Gastroenterology 115: 340– 347.

20. Crabtree, J. E.,, S. Perry,, A. Moran,, P. Peichl,, D. S. Tompkins,, and I. J. D. Lindley. 1994>. Neutrophil IL-8 secretion induced by Helicobacter pylori. Am. J. Gastroenterol. 89: 1337.

21. Crabtree, J. E.,, B. Rembacken,, I. J. D. Lindley,, and A. P. Moran. 1995. Preferential induction of interleukin-8 from gastric epithelial cell lines by Helicobacter pylori lipopolysaccharide. Gut( Suppl. 1) 37: A31.

22. Cunningham, M. D.,, C. Seachord,, K. Ratcliffe,, B. Bainbridge,, A. Aruffo,, and R. P. Darveau. 1996. Helicobacter pylori and Porphyromonas gingivalis lipopolysaccharides are poorly transferred to recombinant soluble CD14. Infect. Immun. 64: 3601– 3608.

23. Darveau, R. P.,, M. D. Cunningham,, T. Bailey,, C. Seachord,, K. Ratcliffe,, B. Bainbridge,, M. Dietsch,, R. C. Page,, and A. Aruffo. 1995. Ability of bacteria associated with chronic inflammatory disease to stimulate E-selectin expression and promote neutrophil adhesion. Infect. Immun. 63: 1317– 1311.

24. Doig, P.,, B. L. de Jonge,, R. A. Aim,, E. D. Brown,, M. Uria-Nickelsen,, B. Noonan,, S. D. Mills,, P. Tummino,, G. Carmel,, B. C. Guild,, D. T. Moir,, G. F. Vovis,, and T. J. Trust. 1999. Helicobacter pylori physiology predicted from genomic comparison of two strains. Microbiol. Mol. Biol. Rev. 63: 675– 707.

25. Edwards, N. J.,, M. Monteiro,, E. J. Walsh,, A. P. Moran,, I. S. Roberts,, and N. J. High. 2000. Lewis X structures in the O antigen side-chain promote adhesion of Helicobacter pylorito the gastric epithelium. Mol. Microbiol. 35: 1530– 1539.

26. Faller, G.,, H. Steininger,, B. J. Appelmelk,, and T. Kirchner. 1998. Evidence of novel pathogenic pathways for the formation of antigastric autoantibodies in Helicobacter pylori gastritis. J. Clin. Pathol. 51: 244– 245.

27. Faller, G.,, H. Steininger,, J. Kranzlein,, H. Maul,, T. Kerkau,, J. Hensen,, E. G. Hahn,, and T. Kirchner. 1997. Antigastric autoantibodies in Helicobacter pylori infection: implications of the histological and clinical parameters of gastritis. Gut 41: 619– 623.

28. Ge, Z.,, N. W. C. Chan,, M. M. Palcic,, and D. E. Taylor. 1997. Cloning and heterologous expression of an α1,3-fuco-syltransferase gene from the gastric pathogen Helicobacter pylori. J. Biol. Chem. 272: 21357– 21363.

29. Goldberg, J. B.,, A. Wright,, J. Ramakrishna,, A. Moran,, D. Kersulyte,, and D. E. Berg. 1996. Cloning of the lipopolysaccharide (LPS)-core gene, rfaC, from Helicobacter pylori. Gut( Suppl. 2) 39: A69.

30. Guruge, J. L.,, P. G. Falk,, R. G. Lorenz,, M. Dans,, H.-P. Wirth,, M. J. Blaser,, D. E. Berg,, and G.J. I. Gordon. 1998. Epithelial attachment alters the outcome of Helicobacter pylori infection. Proc. Natl. Acad. Sci. USA 95: 3925– 3930.

31. Heneghan, M. A.,, C. F. McCarthy,, and A. P. Moran,. 1998. Is colonisation of gastric mucosa by Helicobacter pylori strains expressing Lewis x and y epitopes dependent on host secretor status?, p. 473– 477. In A. J. Lastovica,, D. G. Newell,, and E. E. Lastovica (ed.), Campylobacter, Helicobacter, and Related Organisms. Institute of Child Health and University of Cape Town, Cape Town, South Africa.

32. Heneghan, M. A.,, C. F. McCarthy,, and A. P. Moran. 2000. Relationship of blood group determinants on Helicobacter pylori lipopolysaccharide with host Lewis phenotype and inflammatory response. Infect. Immun. 68: 937– 941.

33. Heneghan, M. A.,, A. P. Moran,, K. M. Feeley,, E. L. Egan,, J. Goulding,, C. E. Connolly,, and C. F. McCarthy. 1998. Effect of host Lewis blood group antigen expression on Helicobacter pylori colonisation density and the consequent inflammatory response. FEMS Immunol. Med. Microbiol. 20: 257– 266.

34. Hoist, O.,, A. J. Ulmer,, H. Brade,, H.-D. Flad,, and E. T. Rietschel. 1996. Biochemistry and cell biology of bacterial endotoxins. FEMS Immunol. Med. Microbiol. 16: 83– 104.

35. Hynes, S. O.,, S. Hirmo,, T. Wadström,, and A. P. Moran. 1999. Differentiation of Helicobacter pylori isolates based on lectin binding of cell extracts in an agglutination assay. J. Clin. Microbiol. 37: 1994– 1998.

36. Hynes, S. O.,, H. Sjunnesson,, E. Sturegård,, T. Wadström,, and A. P. Moran,. 1999. A relationship between the expression of high molecular weight lipopolysaccharide by Helicobacter pylori and colonizing ability in mice, abstr. HP43, p. 158. In H. L. T. Mobley,, I. Nachamkin,, and D. McGee (ed.), Abstracts of the 10th International Workshop on Campylobacter, Helicobacter and Related Organisms. University of Maryland, Baltimore, Md.

37. Keenan, J.,, T. Day,, S. Neal,, B. Cook,, G. Perez-Perez,, R. Allardyce,, and P. Bagshaw. 2000. A role for the bacterial outer membrane in the pathogenesis of Helicobacter pylori. FEMS Microbiol. Lett. 182: 259– 264.

38. Kidd, M.,, K. Miu,, L. H. Tang,, G. I. Perez-Perez,, M.J. Blåser,, A. Sandor,, and I. M. Modlin. 1997. Helicobacter pylori lipopolysaccharide stimulates histamine release and DNA synthesis in rat enterochromaffin-like cells. Gastroenterology 113: 1110– 1117.

39. Knirel, Y. A.,, N. A. Kocharova,, S. O. Hynes,, G. Widmalm,, L. P. Andersen,, P.-E. Jansson,, and A. P. Moran. 1999. Structural studies on lipolysaccharides of serologically non-typable strains of Helicobacter pylori, AF1 and 007, expressing Lewis antigenic determinants. Eur. J. Biochem. 266: 123– 131.

40. Kocharova, N. A.,, K. A. Knirel,, G. Widmalm,, P.-E. Jansson,, and A. P. Moran. 2000. Structure of an atypical O-antigen polysaccharide of Helicobacter pylori containing a novel monosaccharide 3-C-methyl-D-mannose. Biochemistry 39: 4755– 4760.

41. Kwon, D.-H.,, J.-S. Woo,, C.-L. Perng,, M. F. Go,, D. Y. Graham,, and F. A. K. El-Zaatari. 1998. The effect of galE gene inactivation on lipopolysaccharide profile of Helicobacter pylori. Curr. Microbiol. 37: 144– 148.

42. Lamarque, D.,, A. P. Moran,, Z. Szepes,, J. C. Delchier,, and B. J. R. Whittle. 2000. Cytotoxicity associated with induction of nitric oxide synthase in rat duodenal epithelial cells in vivo by lipopolysaccharide of Helicobacter pylori: inhibition by superoxide dismutase. Br. J. Pharmacol. 130: 1531– 1538.

43. Lamarque, D.,, Z. Szepes,, A. P. Moran,, J. C. Delchier,, and B. J. R. Whittle. 1997. A purified lipopolysaccharide (LPS) from Helicobacter pylori (Hp) causes epithelial cell damage and induction of nitric oxide synthase in rat duodenum and colon. Ir. J. Med. Sci.( Suppl. 3) 166: 11.

44. Liang-Takasaki, C.-J.,, P. H. Mäkelä,, and L. Leive. 1982. Phagocytosis of bacteria by macrophages: changing the carbohydrate of lipopolysaccharide alters interaction with complement and macrophages. J. Immunol. 128: 1229– 1235.

45. Ljungh, A.,, A. P. Moran,, and T. Wadström. 1996. Interactions of bacterial adhesins with extracellular matrix and plasma proteins: pathogenic implications and therapeutic possibilities. FEMS Immunol. Med. Microbiol. 16: 117– 126.

46. Logan, S. M.,, J. W. Conlan,, M. A. Monteiro,, W. W. Wakarchuk,, and E. Altman. 2000. Functional genomics of Helicobacter pylori: identification of a beta-l,4-galactosyltransferase and generation of mutants with altered lipopolysaccharide. Mol. Microbiol. 35: 1156– 1167.

47. Ma, J. Y.,, K. Borch,, S. E. Sjöstrand,, L. Janzon,, and S. Mårdh. 1994. Positive correlation between H,K-adenosine triphosphate autoantibodies and Helicobacter pylori antibodies in patients with pernicious anaemia. Scand. J. Gastroenterol. 29: 961– 965.

48. Mai, U. E. H.,, G. I. Perez-Perez,, L. M. Wahl,, S. M. Wahl,, M. J. Blaser,, and P. D. Smith. 1991. Soluble surface proteins from Helicobacter pylori activate monocytes/macrophages by lipopolysaccharide-independent mechanism. J. Clin. Invest. 87: 894– 900.

49. Marais, A.,, G. L. Mendz,, S. L. Hazell,, and F. Megraud. 1999. Metabolism and genetics of Helicobacter pylori: the genome era. Microbiol. Mol. Biol. Rev. 63: 642– 674.

50. Marshall, D. G.,, S. O. Hynes,, D. C. Coleman,, C. A. O'Mor-ain,, C. J. Smyth,, and A. P. Moran. 1999. Lack of a relationship between Lewis antigen expression and cagA, CagA, vacA and VacA status of Irish Helicobacter pylori isolates. FEMS Immunol. Med. Microbiol. 24: 79– 90.

51. Martin, S. L.,, M. R. Edbrooke,, T. C. Hodgman,, D. H. van den Eijnden,, and M. I. Bird. 1999. Lewis X biosynthesis in Helicobacter pylori. Molecular cloning of an α(l,3)-fucosyl-transferase gene. J. Biol. Chem. 272: 21349– 21356.

52. McGowan, C. C.,, A. Necheva,, S. A. Thompson,, T. L. Cover,, and M. J. Blaser. 1998. Acid-induced expression of an LPS-associated gene in Helicobacter pylori. Mol. Microbiol. 30: 19– 31.

53. Mills, S. D.,, L. A. Kurjancyzk,, and J. L. Penner. 1992. Antigenicity of Helicobacter pylori lipopolysaccharides. Infect. Immun. 30: 3175– 3180.

54. Monteiro, M. A.,, B. J. Appelmeik,, D. A. Rasko,, A. P. Moran,, L. L. McLean,, K. H. Chan,, F. S. St. Michael,, S. M. Logan,, J. O'Rourke,, A. Lee,, S. O. Hynes,, D. E. Taylor,, and M. B. Perry. 2000. Lipopolysaccharide structures of Helicobacter pylori genomic strains 26695 and J99, mouse model H. pylori Sydney strain, H. pylori P466 carrying sialyl-Lewis X, and H. pylori UA915 expressing Lewis B. Classification of H. pylori lipopolysaccharides into glycotype families. Eur. J. Biochem. 267: 305– 320.

55. Monteiro, M. A.,, K. H. N. Chan,, D. A. Rasko,, D. E. Taylor,, P. Y. Zheng,, B. J. Appelmelk,, H. P. Wirth,, M. Q. Yang,, M. J. Blaser,, S. O. Hynes,, A. P. Moran,, and M. B. Perry. 1998. Simultaneous expression of type 1 and type 2 Lewis blood group antigens by Helicobacter pylori lipopolysaccharides. Molecular mimicry between H. pylori lipopolysaccharides and human gastric epithelial cell surface glycoforms. J. Biol. Chem. 273: 11533– 11543.

56. Monteiro, M. A.,, D. Rasko,, D. E. Taylor,, and M. B. Perry. 1998. Glucosylated N-acetyllactosamine O-antigen chain in the lipopolysaccharide from Helicobacter pylori strain UA861. Glycobiology 8: 107– 112.

57. Moran, A. P. 1994. Structure-bioactivity relationships of bacterial endotoxins. J. Toxicol. Toxin Rev. 14: 47– 83.

58. Moran, A. P. 1995. Cell surface characteristics of Helicobacter pylori. FEMS Immunol. Med. Microbiol. 10: 271– 280.

59. Moran, A. P. 1996. The role of lipopolysaccharide in Helicobacter pylori pathogenesis. Aliment. Pharmacol. Ther. (Suppl. l) 10: 39– 50.

60. Moran, A. P. 1996. Pathogenic properties of Helicobacter pylori. Scand. J. Gastroenterol. ( Suppl. 215) 31: 22– 31.

61. Moran, A. 1998. The products of Helicobacter pylori that induce inflammation. Eur. J. Gastroenterol. Hepatol.( Suppl. 1) 10: S3– S8.

62. Moran, A. P. 1999. Helicobacter pylori lipopolysaccharide-mediated gastric and extragastric pathology. J. Physiol. Pharmacol. 50: 787– 805.

63. Moran, A. P. 2001. Unpublished data.

64. Moran, A. P.,, B. J. Appelmelk,, and G. O. Aspinall. 1996. Molecular mimicry of host structures by lipopolysaccharides of Campylobacter and Helicobacter spp.: implications in pathogenesis. J. Endotoxin Res. 3: 521– 531.

65. Moran, A. P.,, and G. O. Aspinall. 1998. Unique structural and biological features of Helicobacter pylori lipopolysaccharides. Prog. Clin. Biol. Res. 397: 37– 49.

66. Moran, A. P.,, I. M. Helander,, and T. U. Kosunen. 1992. Compositional analysis of Helicobacter pylori rough-form lipopolysaccharides. J. Bacteriol. 174: 1370– 1377.

67. Moran, A. P.,, S. O. Hynes,, and M. A. Heneghan. 1999. Mimicry of blood group antigen A by Helicobacter mustelae and Helicobacter pylori. Gastroenterology 116: 504– 505.

68. Moran, A. P.,, Y. A. Knirel,, N. A. Kocharova,, S. O. Hynes,, G. Widmalm,, L. P. Andersen,, and P.-E. Jansson. 1999. Lipopolysaccharides of serologically non-typable strains of Helicobacter pylori. Gut( Suppl. III) 45: A7.

69. Moran, A. P.,, Y. A. Knirel,, S. N. Senchenkova,, G. Widmalm,, S. O. Hynes,, B. Lindner,, and P.-E. Jansson. Acid-induced phase variation in Lewis blood group antigen expression by Helicobacter pylori lipopolysaccharides. Phenotypic variation in molecular mimicry between H. pylori lipopolysaccharides and human gastric epithelial cell surface glycoforms. Submitted for publication.

70. Moran, A. P.,, P. Kuusela,, and T. U. Kosunen. 1993. Interaction of Helicobacter pylori with extracellular matrix proteins. J. Appl. Bacteriol. 75: 184– 189.

71. Moran, A. P.,, B. Lindner,, and E. J. Walsh. 1997. Structural characterization of the lipid A component of Helicobacter pylori rough- and smooth-form lipopolysaccharides. J. Bacteriol. 179: 6453– 6463.

72. Moran, A. P.,, J. J. McGovern,, B. Lindner,, and E. J. Walsh. 1996. Structural analysis of lipid A from Helicobacter pylori rough- and smooth-form LPS. J. Endotoxin Res.( Suppl. 1) 3: 35.

73. Moran, A. P.,, M. A. Prendergast,, and B. J. Appelmelk. 1996. Molecular mimicry of host structures by bacterial lipopolysaccharides and its contribution to disease. FEMS Immunol. Med. Microbiol. 16: 105– 115.

74. Moran, A. P.,, E. Sturegaârd,, H. Sjunnesson,, T. Wadström,, and S. O. Hynes. 2000. The relationship between O-chain expression and colonisation ability of Helicobacter pylori in a mouse model. FEMS Immunol. Med. Microbiol. 29: 263– 270.

75. Moran, A. P.,, and T. Wadström. 1994. Bacterial pathogenic factors. Curr. Opin. Gastroenterol. (Suppl. 1) 10: 17– 21.

76. Moran, A. P.,, and T. Wadström. 1998. Pathogenesis of Helicobacter pylori. Curr. Opin. Gastroenterol.( Suppl. 1) 14: S9– S14.

77. Moran, A. P.,, and E. J. Walsh. 1993. In vitro production of endotoxin by the gastroduodenal pathogen Helicobacter pylori—relevance to serotyping. Ir. J. Med. Sci. 162: 384.

78. Moran, A. P.,, and E. J. Walsh. 1993. Expression and electrophoretic characterization of smooth-form lipopolysaccharides of Helicobacter pylori. Acta Gastro-Enterol. Belg. 56( Suppl): 98.

79. Moran, A. P.,, G. O. Young,, and A.J. Lastovica. 1998. Pepsinogen induction by Helicobacter pylori lipopolysaccharides. Gut( Suppl. 2) 43: A15.

80. Muotiala, A.,, I. M. Helander,, L. Pyhälä,, T. U. Kosunen,, and A. P. Moran. 1992. Low biological activity of Helicobacter pylori lipopolysaccharide. Infect. Immun. 60: 1714– 1716.

81. Negrini, R.,, L. Lisato,, I. Zanella,, L. Cavazzini,, S. Gullini,, V. Villanacci,, C. Poiesi,, A. Albertini,, and S. Ghielmi. 1991. Helicobacter pylori infection induces antibodies cross-reacting with human gastric mucosa. Gastroenterology 101: 437– 445.

82. Negrini, R.,, A. Savio,, C. Poiesi,, B. J. Appelmelk,, F. Buffoli,, A. Paterlini,, P. Cesari,, M. Graffeo,, D. Vaira,, and G. Franzin. 1996. Antigenic mimicry between Helicobacter pylori and gastric mucosa in the pathogenesis of body atrophic gastritis. Gastroenterology 111: 655– 665.

83. Nielsen, H.,, S. Birkholz,, L. P. Andersen,, and A. P. Moran. 1994. Neutrophil activation by Helicobacter pylori lipopoly-saccharides. J. Infect. Dis. 170: 135– 139.

84. Ootsuba, C.,, T. Okumura,, N. Takahashi,, H. Wakebe,, K. Imagawa,, M. Kikuchi,, and Y. Kohgo. 1997. Helicobacter pylori lipopolysaccharide inhibits acid secretion in pylorus-ligated conscious rats. Biochem. Biophys. Res. Comtnun. 236: 532– 537.

85. Pece, S.,, D. Fumarola,, G. Giuliani,, E. Jirillo,, and A. P. Moran. 1995. Activity in the Limulus amebocyte lysate assay and induction of tumour necrosis factor by diverse Helicobacter pylori lipopolysaccharide preparations. J. Endotoxin Res. 2: 455– 462.

86. Pece, S.,, C. Messa,, D. Caccavo,, G. Giuliani,, B. Greco,, D. Fumarola,, P. Berloco,, A. Di Leo,, E. Jirillo,, and A. P. Moran. 1997. Serum antibody response against Helicobacter pylori NCTC 11637 smooth- and rough-lipopolysaccharide phenotypes in patients with H. pylori-related gastropathy. J. Endotoxin Res. 4: 383– 390.

87. Perez-Perez, G. L.,, and M.J. Blaser. 1987. Conservation and diversity of Campylobacter pyloridis major antigens. Infect. Immun. 55: 1256– 1263.

88. Perez-Perez, G. I.,, V. L. Shepherd,, J. D. Morrow,, and M. J. Blaser. 1995. Activation of human THP-1 cells and rat bone marrow-derived macrophages by Helicobacter pylori lipopolysaccharide. Infect. Immun. 63: 1183– 1187.

89. Piotrowski, J.,, E. Piotrowski,, D. Skrodzka,, A. Slomiany,, and B. Slomiany. 1997. Induction of acute gastritis and epithelial apoptosis by Helicobacter pylori lipopolysaccharide. Scand. J. Gastroenterol. 32: 203– 211.

90. Piotrowski, J.,, A. Slomiany,, and B. Slomiany. 1993. Inhibition of gastric mucosal mucin receptor by Helicobacter pylori lipopolysaccharide. Biochem. Mol. Biol. Int. 31: 1051– 1058.

91. Rasko, D. A.,, G. Wang,, M. M. Palcic,, and D. E. Taylor. 2000. Cloning and characterization of the α(l,3/4)-fucosyl-transferase of Helicobacter pylori. J. Biol. Chem. 275: 4988– 4994.

92. Rieder, G.,, R. A. Hätz,, A. P. Moran,, A. Walz,, M. Stolte,, and G. Enders. 1997. Role of adherence in interleukin-8 induction in Helicobacter pylori-associated gastritis. Infect. Immun. 65: 3622– 3630.

93. Rietschel, E. T.,, L. Brade,, O. Holst,, V. A. Kulshin,, B. Lindner,, A. P. Moran,, U. F. Schade,, U. Zähringer,, and H. Brade,. 1990. Molecular structure of bacterial endotoxin in relation to bio-activity, p. 15– 32. In A. Nowotny,, J. J. Spitzer,, and E. J. Ziegler (ed.), Endotoxin Research Series, vol. 1. Cellular and Molecular Aspects of Endotoxin Reactions. Elsevier Science, Amsterdam, The Netherlands.

94. Rietschel, E. T.,, L. Brade,, U. Schade,, U. Seydel,, U. Zähringer,, O. Holst,, H.-M. Kuhn,, V. A. Kulschin,, A. P. Moran,, and H. Brade,. 1991. Bacterial endotoxins: relationships between chemical structure and biological activity of the inner core-lipid A domain, p. 209– 217. In E. Z. Ron, and S. Rottem (ed.), Microbial Surface Components and Toxins in Relation to Pathogenesis. Plenum Press, New York, N.Y.

95. Ryan, K. A.,, A. P. Moran,, S. O. Hynes,, T. Smith,, D. Hyde,, C. A. O'Morain,, and M. Maher. 2000. Genotyping of cagA and vacA, Lewis antigen status, and anlaysis of the poly-(C) tract in the a(l,3)-fucosyltransferase gene of Irish Helicobacter pylori isolates. FEMS Immunol. Med. Microbiol. 28: 113– 119.

96. Sakamoto, J.,, T. Watanabe,, T. Tokumaru,, H. Takagi,, H. Nakazato,, and K. O. Lloyd. 1989. Expression of Lewis a, Lewis h, Lewis b, Lewis y, sialyl-Lewis a, and sialyl-Lewis x blood group antigens in human gastric carcinoma and in normal gastric tissue. Cancer Res. 49: 745– 752.

97. Saunders, N. J.,, J. F. Peden,, D. W. Hood,, and E. R. Moxon. 1998. Simple sequence repeats in the Helicobacter pylori genome. Mol. Microbiol. 27: 1091– 1098.

98. Semeraro, N.,, P. Montemurro,, C. Piccoli,, V. Muolo,, M. Colucci,, G. Giuliani,, D. Fumarola,, S. Pece,, and A. P. Moran. 1996. Effect of Helicobacter pylori lipopolysaccharide (LPS) and LPS-derivatives on the production of tissue factor and plasminogen activator inhibitor type 2 by human blood mononuclear cells. ]. Infect. Dis. 174: 1255– 1260.

99. Simoons-Smit, I. M.,, B. J. Appelmelk,, T. Verboom,, R. Negrini,, J. L. Penner,, G. O. Aspinall,, A. P. Moran,, S. Fei Fei,, S. Bi-Shan,, W. Rudnica,, A. Savio,, and J. de Graaff. 1996. Typing of Helicobacter pylori with monoclonal antibodies against Lewis antigens in lipopolysaccharide. J. Clin. Microbiol. 34: 2196– 2200.

100. Slomiany, B. L.,, Y. H. Liau,, R. A. Lopez,, J. Piotrowski,, A. Czajkowski,, and A. Slomiany. 1992. Effect of Helicobacter pylori lipopolysaccharide on the synthesis of sulfated gastric mucin. Biochem. Int. 27: 687– 697.

101. Slomiany, B. L.,, J. Piotrowski,, G. Rajiah,, and A. Slomiany. 1991. Inhibition of gastric mucosal laminin receptor by Helicobacter pylori lipopolysaccharide: effect of nitecapone. Gen. Pharmacol. 22: 1063– 1069.

102. Suda, Y.,, T. Ogawa,, W. Kashihara,, M. Oikawa,, T. Shimoyama,, T. Hayashi,, T. Tamura,, and S. Kusumoto. 1997. Chemical structure of lipid A from Helicobacter pylori strain 2061 lipopolysaccharide. J. Biochem. 121: 1129– 1133.

103. Tarkkanen, J.,, T. U. Kosunen,, and E. Saksela. 1993. Contact of lymphocytes with Helicobacter pylori augments natural killer cell activity and induces production of gamma interferon. Infect. Immun. 61: 3012– 3016.

104. Taylor, D. E.,, D. A. Rasko,, R. Sherburne,, C. Ho,, and L. D. Jewell. 1998. Lack of correlation between Lewis antigen expression by Helicobacter pylori and gastric epithelial cells in infected patients. Gastroenterology 115: 1113– 1122.

105. Terres, A. M.,, J. M. Pajares,, A. M. Hepkins,, A. Murphy,, A. Moran,, A. W. Baird,, and D. Kelleher. 1998. Helicobacter pylori disrupts epithelial barrier function in a process inhibited by protein kinase C activators. Infect. Immun. 66: 2943– 2950.

106. Tomb, J.-F.,, O. White,, A. R. Kerlavage,, R. A. Clayton,, G. G. Sutton,, R. D. Fleischmann,, K. A. Ketchum,, H. P. Klenk,, S. Gill,, B. A. Dougherty,, K. Nelson,, J. Quackenbush,, L. Zhou,, E. F. Kirkness,, S. Peterson,, B. Loftus,, D. Richardson,, R. Dodson,, H. G. Khalak,, A. Glodek,, K. McKenney,, L. M. Fitzgerald,, N. Lee,, M. D. Adams,, E. K. Hickey,, D. E. Berg,, J. D. Gocayne,, T. R. Utterback,, J. D. Peterson,, J. M. Kelley,, M. D. Cotton,, J. M. Weidman,, C. Fujii,, C. Bowman,, L. Watthey,, E. Wallin,, W. S. Hayes,, M. Borodovsky,, P. D. Karp,, H. O. Smith,, C. M. Fräser,, and J. C. Venter. 1997. The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature 388: 539– 547.

107. Trust, T. J.,, P. Doig,, L. Emödy,, Z. Kienle,, T. Wadström,, and P. O'Toole. 1991. High affinity binding of the basement membrane proteins collagen type IV and laminin to the gastric pathogen Helicobacter pylori. Infect. Immun. 59: 4398– 4404.

108. Valkonen, K. H.,, M. Ringner,, Ä. Ljungh,, and T. Wadström. 1993. High affinity binding of laminin by Helicobacter pylori: evidence for a lectin-like interaction. FEMS Immunol. Med. Microbiol. 7: 29– 38.

109. Valkonen, K. H.,, T. Wadström,, and A. P. Moran. 1994. Interaction of lipopolysaccharides of Helicobacter pylori with basement membrane protein laminin. Infect. Immun. 62: 3640– 3648.

110. Valkonen, K. H.,, T. Wadström,, and A. P. Moran. 1997. Identification of the N-acetylneuraminyllactose-specific laminin-binding protein of Helicobacter pylori. Infect. Immun. 65: 916– 923.

111. Walsh, E. J.,, and A. P. Moran. 1996. Serological analysis of the core region of Helicobacter pylori lipopolysaccharide. Gut( Suppl. 2) 39: A71– A72.

112. Walsh, E. J.,, and A. P. Moran. 1997. Influence of medium composition on the growth and antigen expression of Helicobacter pylori. J. Appl. Microbiol. 83: 67– 75.

113. Wang, G.,, D. A. Rasko,, R. Sherburne,, and D. E. Taylor. 1999. Molecular genetic basis for the variable expression of Lewis Y in Helicobacter pylori: analysis of the α(l,2)-fucosyl-transferase gene. Mol. Microbiol. 31: 1265– 1274.

114. Weintraub, A.,, U. Zähringer,, H. W. Wollenweber,, U. Seydel,, and E. T. Rietschel. 1989. Structural characterization of the lipid A component of Bacteroides fragilis strain NCTC 9343 lipopolysaccharide. Eur. J. Biocbem. 183: 425– 431.

115. Wirth, H. P.,, M. Yang,, M. Karita,, and M. J. Blaser. 1996. Expression of the human cell surface glycoconjugates Lewis X and Lewis Y by Helicobacter pylori isolates is related to cagA status. Infect. Immun. 64: 4598– 4605.

116. Wirth, H. P.,, M. Yang,, R. M. Peek,, J. Höök-Nikanne,, M. Fried,, and M. J. Blaser. 1999. Phenotypic diversity in Lewis expression of Helicobacter pylori isolates from the same host. J. Lab. Clin. Med. 133: 488– 500.

117. Wirth, H. P.,, M. Yang,, R. M. Peek,, K. T. Tham,, and M. J. Blaser. 1997. Helicobacter pylori Lewis expression is related to the host Lewis phenotype. Gastroenterology 113: 1091– 1098.

118. Young, G. O.,, A. J. Lastovica,, S. Brown,, J. J. McGovern,, and A. Moran,. 1996. Effect of pepsinogen release of various sub-fractions of H. pylori lipopolysaccharide, p. 697– 700. In D. Newell,, J. M. Ketley,, and R. A. Feldman (ed.), Campylobacters, Helicobacters and Related Organisms. Plenum Press, New York, N.Y.

119. Young, G. O.,, N. Stemmet,, A. Lastovica,, E. L. van der Merwe,, J. A. Louw,, I. M. Modlin,, and I. N. Marks. 1992. Helicobacter pylori lipopolysaccharide stimulates gastric mucosal pepsinogen secretion. Aliment. Pharmacol. Ther. 6: 169– 177.