Bacterial Genotoxins as the Interphase Between DNA Damage and Immune Response

Abstract

Bacterial genotoxins are a class of molecules that have the ability to enter the nucleus of a host cell and cause DNA damage by introducing single-and double-strand DNA breaks, leading to various effects, including activation of DNA damage response, senescence, apoptosis, and genetic aberrations. There is emerging evidence for an intricate connection between the DNA damage response and immunity, and it is becoming increasingly clear that bacterial genotoxins can act as potent immunomodulatory factors, which bacteria use in order to tailor the host immune response. This chapter will review some of the basic structural and functional characteristics of bacterial genotoxins and the internalization pathway used to reach the host DNA within the nuclear compartment. Special focus will be given to the connection between the genotoxin-induced DNA damage response and modulation of the host immune responses. Since it is not entirely clear what is the evolutionary advantage for bacteria that express these effectors, the possibility that they might play a role in influencing host immune response in order to promote stealth invasion and establishment of persistent infections will be explored.