Type IX class utilizing cell signals for organizing toxin-antitoxin systems

The toxin-antitoxin (TA) field continues to advance rapidly, especially given the recognition of TA systems as one of the most prevalent phage defenses. These systems are omnipresent in both bacteria and archaea and are currently classified into eight types. Here, we propose an additional type IX class, in which either the toxin or antitoxin utilizes nucleotide-based signaling. By establishing the new type IX TA system, the framework for the organization of TA systems, which is based on the diverse biochemical functions of both the toxins and antitoxins across the nine types, will be refined and aid in their discovery and understanding. In addition, we highlight the increasing evidence that TA systems are related to persistence and are activated by conformational changes in protein complexes.