Genotypic and Phenotypic Variation of Lewis Antigen Expression in Geographically Diverse Helicobacter pylori Isolates

Abstract

Helicobacter pylori are a persistent colonizer of the human gastric mucosa, which can lead to the development of peptic ulcer disease and gastric adenocarcinomas. However, H. pylori can asymptomatically colonize a host for years. One factor that has been hypothesized to contribute to such persistence is the production of Lewis (Le) antigens in the lipopolysaccharide layer of the bacterial outer membrane as a form of molecular mimicry, because humans also express these antigens on their gastric mucosa. Humans and H. pylori both are polymorphic for Le expression, which is driven in H. pylori by variation at the Le synthesis loci. In this report, we sought to characterize Le genotypic and phenotypic variation in geographically diverse H. pylori isolates. From patients undergoing endoscopy in 29 countries, we determined Le phenotypes of 78 H. pylori strains and performed genotyping of the galT and β-(1,3)galT loci in 113 H. pylori strains. Le antigen phenotyping revealed a significant (p < .0001) association between type 1 (Le(a) and Le(b) ) expression and strains of East Asian origin. Genotyping revealed a significant correlation between strain origin and the size of the promoter region upstream of the Le synthesis gene, galT (p < .0001). These results indicate that the heterogeneity of human Le phenotypes is reflected in their H. pylori colonizing strains and suggest new loci that can be studied to assess the variation of Le expression.