Epigenetic Programming by Microbial Pathogens and Impacts on Acute and Chronic Disease

Epigenetic programming of the pathogen and the host can have a marked influence on the development and progression of acute and chronic disease. Bacterial pathogenesis may be viewed as a developmental program similar to that of cell differentiation and development in eukaryotes. Bacterial epigenetic programming is imparted by DNA methylation, whereby the virulence traits expressed by a pathogen may depend on the cumulative interactions between the microbe and its environment. Such bacterial “memory” provides a means for adaptation to the varied subsequent microenvironments encountered during the infective process. DNA methylation can affect DNA–protein interactions and resultant gene expression by altering DNA thermodynamic stability and curvature and by methyl-group-mediated steric hindrance. Some of these epigenetic interactions can form heritable DNA methylation patterns in the microbial genome that control gene expression in their progeny cells. Microbes can also stimulate heritable changes in the host epigenome via infection-associated alterations to host epigenetic determinants including DNA methylation, histone modifications, chromatin-associated complexes, and noncoding RNA-mediated silencing. The resultant changes in host chromatin remodeling and gene expression may be localized and/or systemic due to direct microbe-to-host cell communication or via dissemination of microbial-host signaling. Thus, the role of epigenetics in host–microbe interactions may be the nexus of many pathological syndromes even though there may be no apparent direct link between infection and disease, providing the basis for the development of novel therapeutics and diagnostic tests for diseases with epigenomic determinants.