Toxin–antitoxin systems as mediators of phage defence and the implications for abortive infection

Bacteria have evolved a broad range of defence mechanisms to protect against infection by their viral parasites, bacteriophages (phages). Toxin-antitoxin (TA) systems are small loci found throughout bacteria and archaea that in some cases provide phage defence. The recent explosion in phage defence system discovery has identified multiple novel TA systems with antiphage activity. Due to inherent toxicity, TA systems are thought to mediate abortive infection (Abi), wherein the host cell dies in response to phage infection, removing the phage, and protecting clonal siblings. Recent studies, however, have uncovered molecular mechanisms by which TA systems are activated by phages, how they mediate toxicity, and how phages escape the defences. These new models reveal dazzling complexity in phage-host interactions and provide further evidence that TA systems do not in all cases inherently perform classic Abi, suggesting an evolved conceptual definition is required.