Helicobacter pylori Restriction-Modification Systems: Roles beyond Genome Protection

One of the important characteristics of Helicobacter pylori is the high degree of allelic diversity and genetic variability, which probably helps it to adapt and colonize within the human host. The genome of H.pylori is rich in restriction-modification (RM) systems, some of which have shown to function as partial systems with only the DNA methyltransferase component being active. In H.pylori strain 26695 hpyAVIBM codes for a phase-variable C5 cytosine methyltransferase. Overexpression of M.HpyAVIBM in E. coli enhances the rate of mutations. The M.HpyAVIB gene itself undergoes random mutations which give rise to variants of M.HpyAVIB with different biochemical properties. Interestingly, changes in the transcriptome were observed on expression of M.HpyAVIB gene in E.coli. M.HpyAVIB suppresses the expression of a number of genes involved in metabolism, motility, and DNA repair and resulted in enhanced mutation rates by changing the expression of genes involved in mismatch repair and SOS pathways. Our results highlight the pleiotropic effects of cytosine methylation by M.HpyAVIB in E.coli. H.pylori is naturally competent and exhibits great strain diversity within its gastric niche. Thus, strain to strain exchange of DNA, and thereby functional methyltransferases, may alter the methylation pattern on the chromosome and possibly the transcriptome.