Preventing toxicity in toxin-antitoxin systems: An overview of regulatory mechanisms

Toxin-antitoxin systems (TAs) are generally two-component genetic modules present in almost every prokaryotic genome. The production of the free and active toxin is able to disrupt key cellular processes leading to the growth inhibition or death of its host organism in absence of its cognate antitoxin. The functions attributed to TAs rely on this lethal phenotype ranging from mobile genetic elements stabilization to phage defense. Their abundance in prokaryotic genomes as well as their lethal potential make them attractive targets for new antibacterial strategies. The hijacking of TAs requires a deep understanding of their regulation to be able to design such approach. In this review, we summarize the accumulated knowledge on how bacteria cope with these toxic genes in their genome. The characterized TAs can be grouped based on the way they prevent toxicity. Some systems rely on a tight control of the expression to prevent the production of the toxin while others control the activity of the toxin at the post-translational level.