Phasevarion mediated random switching of gene expression in Helicobacter Pylori

Many host-adapted bacterial pathogens contain DNA methyltransferases (mod genes) that are subject to phase-variable expression (high-frequency reversible ON/OFF switching of gene expression). In Haemophilus influenzae, Neissera Meningtidis and Neisseria Gonorrhoeae, the random switching of the modA gene, associated with a phase variable type III restriction modification (R-M) system, controls expression of a phase-variable regulon of genes (a “phasevarion”), via differential methylation of the genome in the modA ON and OFF states. Phase variable type III R-M systems are also found in Helicobacter pylori, suggesting that phasevarions may also exist in this intriguing pathogen. Phylogenetic studies on the phase-variable type III modC gene revealed that there are 12 distinct alleles in H. pylori, which differ only in their DNA recognition domain, with the majority containing the C5 allele. Microarray analysis comparing the H. pylori wild-type P12modC5 ON strain to the P12(delta)modC5 mutant revealed that six genes were either up-regulated or down-regulated, some of which were virulence-associated. For example flaA, which encodes a flagella protein important in motility and hopG, which encodes an important outer membrane protein. This study, in conjunction with our previous work, indicates that phasevarions may be a common strategy used by host-adapted bacterial pathogens to randomly switch between “differentiated” cell types. Direct comparison of biological triplicates of wild type and mutant strains