Toxin–antitoxin systems: Classification, biological roles, and applications

Toxin–antitoxin (TA) systems, composed of a stable toxin and a cognate unstable antitoxin, are ubiquitous in the genomes of bacteria and archaea. Under suitable growth conditions, an antitoxin prevents its cognate toxin from inducing toxicity; nonetheless, under stress or plasmid loss, it is either rapidly degraded or downregulated, thereby freeing the toxin to exert its activity toward various targets. Currently, TA systems are classified into eight types based on the nature and mode of action of antitoxins. TA expression is tightly regulated at multiple levels. These systems have various biological roles, including genetic element maintenance, virulence, stress resistance, and phage inhibition. Because of the toxic property of toxins, TA systems have been exploited for biotechnological (e.g., DNA cloning, plasmid maintenance, and counterselection) and medical (e.g., antibacterial drugs, antivirals, and anticancer therapies) applications. Herein, we provided an updated overview of TA systems by focusing on their classification, biological roles, and applications. We also described recent advances in research on TA systems and discussed research perspectives in this field.