Large scale changes in host methylation patterns induced by IncA/C plasmid transformation inVibrio cholerae

DNA methylation is a central epigenetic modification and has diverse biological functions in eukaryotic and prokaryotic organisms alike. The IncA/C plasmid genomes are approximately 150kb in length and harbour three methylase genes, two of which demonstrate cytosine specificity. Transformation of the Vibrio cholerae strain C6706 with the IncA/C plasmid pVC211 resulted in a significant relabelling of the methylation patterns on the host chromosomes. The new methylation patterns induced by transformation with IncA/C plasmid were accepted by the restriction enzymes of the host’s restriction modification (RM) system. These data uncover a novel mechanism by which plasmids can be compatible with a host’s RM system and suggest a possible reason that plasmids of the IncA/C family are broad-host-range. Author summary Antibiotic resistance of bacteria is a growing serious problem worldwidely and the horizontal transfer of multi-drug resistance genes mediated by plasmids within and between species of bacteria is the main reason. In the researches of multi-drug resistance of Vibrio cholerae , I have isolated several IncA/C plasmids. What impressed me most is their ability to accumulate the resistant genes. Moreover, they can transfer with high frequency and are stable in several bacterial species. There are at least three Tra regions on the IncA/C plasmid which containing components of the Type 4 Secretion System and are important for conjugative transfer of plasmids. So the horizontal transfer ability of IncA/C plasmids is reasonable. There are three methylase genes on the small genome of IncA/C plasmids, which demonstrate cytosine specificity and are seldom in bacteria. Their modification target and roles are interesting. Here, we analysed the methylation profiles of the host V. choerae induced by the plasmid pVC211 and found that they were completely changed. In addition to replicons, this may be a novel mechanism that plasmid cross the barrier of the host’s RM system and become broad-host range. Changing the activity of methylase in IncA/C plasmids may be a new way to affect the stability of IncA/C plasmids to eliminate these multidrug-resistant plasmids from bacteria.