Role of epigenetic reprogramming of host genes in bacterial pathogenesis

Abstract

The genomes are regularly targeted by epigenetic regulatory mechanisms (DNA methylation, histone modifications, binding of regulatory proteins) in infected cells. In addition, proteins encoded by microbial genomes may disturb the action of a set of cellular promoters by interacting with the same epi-regulatory machinery. The outcome of this may result in epigenetic dysregulation and subsequent cellular dysfunctions that may manifest in or contribute to the development of pathological changes. How epigenetic methylation decorations on DNA and histones are started and established remains largely unknown. The inherited nature of these processes in regulation of genes suggests that they could play key roles in chronic diseases associated with microbial persistence; they might also explain so-called hit-and-run phenomena in infectious disease pathogenesis. Microbes infecting mammals may cause diseases by causing hyper-methylation of key cellular promoters at CpG di-nucleotides and may induce pathological changes by epigenetic reprogramming of host cells they are interacting with elucidation of the epigenetic consequences of microbe-host interactions may have important therapeutic implications because epigenetic processes can be reverted and elimination of microbes inducing patho-epigenetic changes may prevent disease development.

Keywords: DNA methylation; Epigenetics; Host genome; Microbes.

Figure 1

The figure shows a representative region of genomic DNA. Methylation of cytosine residues is associated with gene silencing. Methylation of certain genomic regions is inherited (imprinting) and is involved in the silencing. Alterations in methylation can also be acquired (e.g. in cancer cells). The region contains repeat-rich, hyper-methylated heterochromatin and an actively transcribed tumor suppressor gene associated with a hypo-methylated CpG island (indicated in red).