Cross talk between bacteria and the host epigenetic machinery

Abstract

Multidisciplinary approaches combining microbiology, cell biology, and genetics have improved our understanding of bacterial diseases by elucidating mechanisms employed by bacteria to manipulate eukaryotic cellular processes. In parallel, research on epigenetics has increased our knowledge about eukaryotic gene expression by providing a mechanistic basis for the amazing plasticity of the genome in response to developmental and environmental cues. These two fields of research have now converged, providing information about the ways in which bacteria shape the epigenome and the mechanisms by which the epigenetic machinery allows the host to respond to colonization by pathogenic or commensal bacteria. The study of this cross talk has revealed remarkable diversity in the mechanisms of action of bacteria on chromatin and has identified epigenetic regulators involved in host responsiveness to bacteria. One powerful strategy used by intracellular pathogens (e.g., Anaplasma, Chlamydia, Ehrlichia, Legionella, Listeria, Mycobacteria, Mycoplasma, Shigella) is the secretion of nucleomodulins that manipulate chromatin structure in the host nucleus. The effects of this dialog are often limited in time, causing transient gene expression changes. However, increasing evidence suggests that certain epigenetic changes triggered by bacterial molecules are long-lasting, leading to the priming of transcriptional responses and the reprogramming of genes involved in inflammation or tolerance, with consequences for reinfection and polymicrobial infections. In addition, the effects of bacteria on the host epigenome may ultimately modify the identity of the cell by breaking epigenetic barriers, leading to cell differentiation, dedifferentiation, or trans-differentiation, thereby potentially contributing to tissue remodeling and emergence of complex diseases.