Epigenetic phase variation in bacterial pathogens

Abstract

Epigenetics is defined as heritable but reversible phenotype that does not involve a change in the DNA sequence. Thus, in a bacterial population epigenetic regulation of gene expression can define the phenotype of an individual cell. For a pathogen, the relevance lies in the phenotype of the infecting population and how this impacts on temporal changes in phenotype during an infection. The focus of this chapter is bacterial epigenetic regulation by DNA methylation and in particular phase variation that is controlled by the maintenance methyltransferase in Escherichia coli and Salmonella. The occurrence, the relevance for virulence, and key concepts of the mechanism are discussed. Our understanding of the relevance is presented based on the roles of the genes that are regulated and by considering the impact of population heterogeneity that occurs as a result of phase variation. More recently, the significance for the virulence of a different range of bacterial pathogens of DNA methyltransferases other than Dam has been identified. This leads to new understanding of possible origins and occurrence of heterogeneity and virulent phenotypes in clonal populations. The contribution of new technologies to explore bacterial methylomes and the challenges in identifying actual epigenetic regulation based on that is discussed. Overall, the current state of knowledge suggests that more examples of epigenetic control in bacteria are yet to be discovered and that this could enhance our understanding of virulence strategies in bacteria.