Bacterial type I toxin-antitoxin systems.

Toxin-antitoxin (TA) loci encode two-component systems that consist of a stable "toxin" whose ectopic overexpression either kills cells or confers growth stasis, and an unstable "antitoxin". TA systems have been initially discovered on plasmids, where they confer stability of maintenance through post-segregational killing (PSK). Plasmid loss results in rapid decrease of antitoxin levels, which allows the stable toxin to kill the plasmid-free cell. Later, TA systems were also found on bacterial and archaeal chromosomes, sometimes in staggering numbers. (1), (2) They are classified into five types depending on the nature and action of the antitoxin. In type I systems, the antitoxin is a small antisense RNA that base-pairs with the toxin encoding mRNA. By contrast, in type II systems, the antitoxin is a protein that interacts post-translationally with the toxin protein. The antitoxin in type III systems is a pseudoknot containing RNA that directly binds the toxin protein. (3), (4) In the recently proposed type IV systems, the protein antitoxin interferes with binding of the toxin to its target rather than inhibiting the toxin directly by binding, (5) whereas the antitoxin protein in type V systems cleaves the toxin-encoding mRNA. (6).