ROLE OF EPIGENETIC MODIFICATION IN REGULATING UROPATHOGENIC ESCHERICHIA COLI VIRULENCE

Abstract

Epigenetic DNA methylation modulates several important bacterial cellular processes, such as mismatch repair, gene regulation, transposition and chromosome replication. Restriction Modification Systems (RMSs) utilise DNA methylation to distinguish between self and non-self DNA but, this epigenetic mark has the potential to alter gene expression and by extension virulence. The objective of this study was to systematically elucidate the role of Type I RMS mediated methylation in Escherichia coli virulence and general physiology. Deletion or replacement of Type I methylation in Uropathogenic E. coli (UPEC) strain UTI89 does not have any effect in specific in vitro assays, such as growth rate, motility, biofilm formation and hemagglutination. This trend continues in far more sensitive assays such as transurethral in vivo infection, RNA-seq and Phenotype Microarray, with no effect observed for Type I methylation. Similar results were observed in UPEC strain CFT073 and non-pathogenic E. coli K12 substrain MG1655, with the exception of one phage and one gene in MG1655 upregulated. To summarise, Type I methylation generally has no effect on any phenotype in three different E. coli strains with distinct Type I methylation patterns, under the conditions tested. This is in contrast with published studies which describe global gene expression changes as a consequence of some RMS mediated DNA methylation.