Type I Restriction–Modification Loci Reveal High Allelic Diversity in Clinical Helicobacter pylori Isolates

Abstract

A remarkable variety of restriction-modification (R-M) systems is found in Helicobacter pylori. Since they encompass a large portion of the strain-specific H. pylori genes and therefore contribute to genetic variability, they are suggested to have an impact on disease outcome. Type I R-M systems comprise three different subunits and are the most complex of the three types of R-M systems. We investigated the genetic diversity and distribution of type I R-M systems in clinical isolates of H. pylori. Sixty-one H. pylori isolates from a Swedish hospital based case-control study and 6 H. pylori isolates of a Swedish population-based study were analyzed using polymerase chain reaction for the presence of the three R-M systems' subunits. Representative gene variants were sequenced. Although the hsdM and hsdR genes appeared conserved in our clinical H. pylori isolates, the sequences of the hsdS loci were highly variable. Despite their sequence diversity, the genes per se were present at high frequencies. We identified a number of novel allelic hsdS variants, which are distinct from corresponding hsdS loci in the sequenced H. pylori strains 26695, J99 and HPAG1. In analyses of paired H. pylori isolates, obtained from the same individuals with a 4-year interval, we observed genetic modifications of hsdS genes in patients with atrophic gastric mucosa. We propose that the genetic variability of hsdS genes in a bacterial population will give rise to new specificities of these enzymes, which might lead to adaptation to an ever-changing gastric environment.