Helicobacter pylori interstrain restriction-modification diversity prevents genome subversion by chromosomal DNA from competing strains

Helicobacter pylori, bacteria that colonize the human gastric mucosa, possess a large number of genes for restriction‐modification (R‐M) systems, and essentially, every strain possesses a unique complement of functional and partial R‐M systems. Nearly half of the H.pylori strains studied possess an active type IIs R‐M system, HpyII, with the recognition sequence GAAGA. Recombination between direct repeats that flank the R‐M cassette allows for its deletion whereas strains lacking hpyIIRM can acquire this cassette through natural transformation. We asked whether strains lacking HpyII R‐M activity can acquire an active hpyIIRM cassette [containing a 1.4 kb kanamycin resistance (aphA) marker], whether such acquisition is DNase sensitive or resistant and whether restriction barriers limit acquisition of chromosomal DNA. Our results indicate that natural transformation and conjugation‐like mechanisms may contribute to the transfer of large (4.8 kb) insertions of chromosomal DNA between H.pylori strains, that inactive or partial R‐M systems can be reactivated upon recombination with a functional allele, consistent with their being contingency genes, and that H.pylori R‐M diversity limits acquisition of chromosomal DNA fragments of ≥1 kb