Similarly, methylation of DNA promoters GDC-941 and origins of replication might provide benefits for the regulation of gene expression [40] and replication [41]. This study confirms prior observations that the mean numbers of active methylases are conserved in H. pylori strains recovered from hosts of different geographical origins [42, 43], suggesting selection for an optimal RMS number across the universe of H. pylori cells [42, 44]. Such selection might be achieved by horizontal gene transfer of RMS genes among H. pylori

strains, with a consequent equilibrium in the number of active methylases. RMSs have been postulated to behave as “”selfish”" mobile genetic elements [27, 45, 46]. Selection favors the maintenance of the system of restriction endonuclease and methylase, because loss of methylase function is lethal. However, intact methylase genes with apparently truncated restriction genes have been observed in completed H. pylori genomes, suggesting that active methylases are involved in the regulation of essential physiological processes that are independent of RMS [47]. However, the process of restriction and methylation Mizoribine mouse might be a dynamic mechanism that can vary in vivo. For example, HpyI methylase (HpyIM) expression varied dramatically within H. pylori cells colonizing the gastric tissue [48]. Dominance of European over Amerindian strains Despite a similar number of

active methylases, hspAmerind strains exhibited higher rates of transformation than hpEurope strains. DNA incorporation into the chromosome during transformation can be divided into three general steps: i) DNA uptake or binding to the cell; ii) degradation of one strand of the invading DNA, and iii) recombination of the remnant DNA fragments into Decitabine the genome [49, 50]. For the first step, extensive evidence supports the fact that H. pylori is highly competent in uptake of “”non-self”" DNA. H. pylori is genetically diverse within a single stomach niche and is subject to a very high rate of intraspecific recombination [11, 14, 51]. Proteins

such as ComB4, ComB7–ComB10 of the type IV secretion system encoded by the comB genes, [52] are homologs to VirB proteins (VirB4, VirB7–VirB10) of A. tumefaciens and resemble their conjugation-like function in H. pylori DNA transformation [53]. Mutations of comB in H. pylori strains abrogate transformation [52, 54]. Whether haplotype learn more differences in the proteins involved in DNA uptake and access to foreign DNA can affect the efficiency of DNA uptake and incorporation, remains to be tested. Step (ii) involves the degradation of one DNA strand and processing of the foreign DNA. Although H. pylori isolates from different bacterial populations exhibit a similar number of methylases, the differences in the cognate recognition sites can explain differences in the “”DNA availability”" as a substrate for recombination.