Phase Variation in Helicobacter pylori Lipopolysaccharide

Abstract

ABSTRACT Helicobacter pylori NCTC 11637 lipopolysaccharide (LPS) expresses the human blood group antigen Lewis x (Le x ) in a polymeric form. Le x is β- d -galactose-(1-4)-[α- l -fucose-(1-3)]-β- 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 α1,3-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 α1,2-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 ) n -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.