CSDB: Search results

References to other databases: GTC:G15465JL, GlycomeDB:1753
Structural formula & atomic coordinates
Sweet-II 3D model
Show glycosyltransferases

Helicobacter pylori is a prevalent bacterial, gastroduodenal pathogen of humans that can express Lewis (Le) and related antigens in the O-chains of its surface lipopolysaccharide. The O-chains of H. pylori are commonly composed of internal Le(x) units with terminal Le(x) or Le(y) units or, in some strains, with additional units of Le(a), Le(b), Le(c), sialyl-Le(x) and H-1 antigens, as well as blood groups A and B, thereby producing a mosaicism of antigenic units expressed. The genetic determination of the Le antigen biosynthetic pathways in H. pylori has been studied, and despite striking functional similarity, low sequence homology occurs between the bacterial and mammalian α(1,3/4)- and α(1,2)-fucosyltransferases. Factors affecting Le antigen expression in H. pylori, that can influence the biological impact of this molecular mimicry, include regulation of fucosyltransferase genes through slipped-strand mispairing, the activity and expression levels of the functional enzymes, the preferences of the expressed enzyme for distinctive acceptor molecules and the availability of activated sugar intermediates. Le mimicry was initially implicated in immune evasion and gastric adaptation by the bacterium, but more recent studies show a role in gastric colonization and bacterial adhesion with galectin-3 identified as the gastric receptor for polymeric Le(x) on the bacterium. From the host defence aspect, innate immune recognition of H. pylori by surfactant protein D is influenced by the extent of LPS fucosylation. Furthermore, Le antigen expression affects both the inflammatory response and T-cell polarization that develops after infection. Although controversial, evidence suggests that long-term H. pylori infection can induce autoreactive anti-Le antibodies cross-reacting with the gastric mucosa, in part leading to the development of gastric atrophy. Thus, Le antigen expression and fucosylation in H. pylori have multiple biological effects on pathogenesis and disease outcome.

molecular mimicry, Helicobacter pylori, Fucosyltransferases, bacterial pathogenesis, Lewis antigens, fucosylation

NCBI PubMed ID: 18279843
Publication DOI: 10.1016/j.carres.2007.12.012
Journal NLM ID: 0043535
Publisher: Elsevier
Correspondence: anthony.moran@nuigalway.ie
Institutions: Department of Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland, Institute for Glycomics, Gold Coast Campus, Griffith University, Queensland 4222, Australia
Methods: NMR, sugar analysis, MS, genetic methods

Both Helicobacter pylori and Campylobacter jejuni are highly prevalent Gram-negative microaerophilic bacteria which are gastrointestinal pathogens of humans; H. pylori colonizes the gastroduodenal compartment and C. jejuni the intestinal mucosa. Although H. pylori causes chronic gastric infection leading to gastritis, peptic ulcers and eventually gastric cancer while C. jejuni causes acute infection inducing diarrhoeal disease, the endotoxin molecules of both bacterial species contrastingly contribute to their pathogenesis and the autoimmune sequelae each induces. Compared with enterobacterial endotoxin, that of H. pylori has significantly lower endotoxic and immuno-activities, the molecular basis for which is the underphosphorylation and underacylation of the lipid A component that interacts with immune receptors. This induction of low immunological responsiveness by endotoxin may aid the prolongation of H. pylori infection and therefore infection chronicity. On the other hand, this contrasts with acute infection-causing C. jejuni where overt inflammation contributes to pathology and diarrhoea production, and whose endotoxin is immunologically and endotoxically active. Futhermore, both H. pylori and C. jejuni exhibit molecular mimicry in the saccharide components of their endotoxins which can induce autoreactive antibodies; H. pylori expresses mimicry of Lewis and some ABO blood group antigens, C. jejuni mimicry of gangliosides. The former has been implicated in influencing the development of inflammation and gastric atrophy (a precursor of gastic cancer), the latter is central to the development of the neurological disorder Guillain-Barre syndrome. Both diseases raise important questions concerning infection-induced autoimmunity awaiting to be addressed.

lipid A, Campylobacter jejuni, molecular mimicry, Helicobacter pylori, bacterial pathogenesis

NCBI PubMed ID: 20593269
Publication DOI: 10.1007/978-90-481-9078-2_10
Publisher: Springer Science+Business Media B.V.
Correspondence: anthony.moran@nuigalway.ie
Editors: Wang X, Quinn PJ
Institutions: Laboratory of Molecular Biochemistry, Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland