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

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 Unpublished data.

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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.

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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.

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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.

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