Phase Variation in Helicobacter pylori Lipopolysaccharide due to Changes in the Lengths of Poly(C) Tracts in α3-Fucosyltransferase Genes

Abstract

ABSTRACT The lipopolysaccharide (LPS) of Helicobacter pylori expresses the Lewis x (Le x ) and/or Le y antigen. We have shown previously that H. pylori LPS displays phase variation whereby an Le x -positive strain yields variants with different LPS serotypes, for example, Le x plus Le y or nonfucosylated polylactosamine. H. pylori has two α3-fucosyltransferase genes that both contain poly(C) tracts. We now demonstrate that these tracts can shorten or lengthen randomly, which results in reversible frameshifting and inactivation of the gene products. We provide genetic and serological evidence that this mechanism causes H. pylori LPS phase variation and demonstrate that the on or off status of α3-fucosyltransferase genes determines the LPS serotypes of phase variants and clinical isolates. The role of the α3-fucosyltransferase gene products in determining the LPS serotype was confirmed by structural-chemical analysis of α3-fucosyltransferase knockout mutants. The data also show that the two α3-fucosyltransferase genes code for enzymes with different fine specificities, and we propose the names futA and futB to designate the orthologs of the H. pylori 26695 α3-fucosyltransferase genes HP0379 and HP0651, respectively. The data also show that the α3-fucosylation in H. pylori precedes α3-fucosyltransferase, an order of events opposite to that which prevails in mammals. Finally, the data provide an understanding at the molecular level of the mechanisms underlying LPS diversity in H. pylori , which may play an important role in adaptation to the host.