title: Phase variation in Helicobacter pylori lipopolysaccharide.
abstract: Helicobacter pylori NCTC 11637 lipopolysaccharide (LPS) expresses the human blood group antigen Lewis x (Le(x)) in a polymeric form. Le(x) is beta-D-galactose-(1-4)-[alpha-L-fucose-(1-3)]-beta-D-acetylglucosamine. Schematically the LPS structure is (Le(x))n-core-lipid A. In this report, we show that Le(x) expression is not a stable trait but that LPS displays a high frequency (0.2 to 0.5%) of phase variation, resulting in the presence of several LPS variants in one bacterial cell population. One type of phase variation implied the loss of alpha1,3-linked fucose, resulting in variants that expressed nonsubstituted polylactosamines (also called the i antigen), i.e., Le(x) minus fucose; LPS: (lactosamine)n-core-lipid A. The switch of Le(x) to i antigen was reversible. A second group of variants arose by loss of polymeric main chain which resulted in expression of monomeric Le(y); LPS: (Le(y))-core-lipid A. A third group of variants arose by acquisition of alpha1,2-linked fucose which hence expressed Le(x) plus Le(y); LPS: (Le(y))(Le(x))n-core-lipid A. The second and third group of variants switched back to the parental phenotype [(Le(x))-core-lipid A] in lower frequencies. Part of the variation can be ascribed to altered expression levels of glycosyltransferase levels as assessed by assaying the activities of galactosyl-, fucosyl-, and N-acetylglucosaminyltransferases. Clearly phase variation increases the heterogeneity of H. pylori, and this process may be involved in generating the very closely related yet genetically slightly different strains that have been isolated from one patient.
authors.affiliation: Department of Medical Microbiology, Vrije Universiteit, Medical School, Amsterdam, The Netherlands. BJ.Appelmelk.mm@med.vu.nl
authors.forename: B J
authors.initials: BJ
authors.lastname: Appelmelk
authors.forename: B
authors.initials: B
authors.lastname: Shiberu
authors.forename: C
authors.initials: C
authors.lastname: Trinks
authors.forename: N
authors.initials: N
authors.lastname: Tapsi
authors.forename: P Y
authors.initials: PY
authors.lastname: Zheng
authors.forename: T
authors.initials: T
authors.lastname: Verboom
authors.forename: J
authors.initials: J
authors.lastname: Maaskant
authors.forename: C H
authors.initials: CH
authors.lastname: Hokke
authors.forename: W E
authors.initials: WE
authors.lastname: Schiphorst
authors.forename: D
authors.initials: D
authors.lastname: Blanchard
authors.forename: I M
authors.initials: IM
authors.lastname: Simoons-Smit
authors.forename: D H
authors.initials: DH
authors.lastname: van den Eijnden
authors.forename: C M
authors.initials: CM
authors.lastname: Vandenbroucke-Grauls
mesh_terms: D000606:Amino Sugars / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000940:Antigenic Variation; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005647:Fucosyltransferases / Q000378:metabolism; D005700:Galactosyltransferases / Q000378:metabolism; D016695:Glycosyltransferases / Q000378:metabolism; D016480:Helicobacter pylori / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007983:Lewis Blood Group Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016256:Lewis X Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008050:Lipid A / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology* / Q000378:metabolism; D018716:Molecular Mimicry / Q000235:genetics / Q000276:immunology; D009154:Mutation; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D011134:Polysaccharides / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000606:Amino Sugars; D000939:Epitopes; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen; C094162:Lewis Y antigen; D008050:Lipid A; D008070:Lipopolysaccharides; D011134:Polysaccharides; C066929:polylactosamine; D016695:Glycosyltransferases; D005647:Fucosyltransferases; D005700:Galactosyltransferases; D017351:N-Acetylglucosaminyltransferases