Cross-Regulations between Bacterial Toxin-Antitoxin Systems: Evidence of an Interconnected Regulatory Network?

Toxin-antitoxin (TA) systems are ubiquitous among bacteria and include stable toxins whose toxicity can be counteracted by RNA or protein antitoxins. They are involved in multiple functions that range from stability maintenance for mobile genetic elements to stress adaptation. Bacterial chromosomes frequently have multiple homologues of TA system loci, and it is unclear why there are so many of them. In this review we focus on cross-regulations between TA systems, which occur between both homologous and nonhomologous systems, from similar or distinct types, whether encoded from plasmids or chromosomes. In addition to being able to modulate RNA expression levels, cross-regulations between these systems can also influence their toxicity. This suggests the idea that they are involved in an interconnected regulatory network.