Type I restriction-modification loci reveal high allelic diversity in clinical Helicobacter pylori isolates.
BACKGROUND
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.


OBJECTIVE
We investigated the genetic diversity and distribution of type I R-M systems in clinical isolates of H. pylori.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Andres
Sönke
S
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Skoglund
Anna
A
Nilsson
Christina
C
Krabbe
Margareta
M
Björkholm
Britta
B
Engstrand
Lars
L
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics*; D015373:Bacterial Typing Techniques; D016000:Cluster Analysis; D015280:DNA Restriction-Modification Enzymes / Q000235:genetics*; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D005838:Genotype; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013548:Sweden
D001426:Bacterial Proteins; D015280:DNA Restriction-Modification Enzymes; D004269:DNA, Bacterial; C113046:HSDS protein, Bacteria; C109829:HsdM protein, Bacteria