Bacterial toxin-antitoxin systems: Translation inhibitors everywhere.

Toxin-antitoxin (TA) systems are composed of two elements: a toxic protein and an antitoxin which is either an RNA (type I and III) or a protein (type II). Type II systems are abundant in bacterial genomes in which they move via horizontal gene transfer. They are generally composed of two genes organized in an operon, encoding a toxin and a labile antitoxin. When carried by mobile genetic elements, these small modules contribute to their stability by a phenomenon denoted as addiction. Recently, we developed a bioinformatics procedure that, along with experimental validation, allowed the identification of nine novel toxin super-families. Here, considering that some toxin super-families exhibit dramatic sequence diversity but similar structure, bioinformatics tools were used to predict tertiary structures of novel toxins. Seven of the nine novel super-families did not show any structural homology with known toxins, indicating that combination of sequence similarity and three-dimensional structure prediction allows a consistent classification. Interestingly, the novel super-families are translation inhibitors similar to the majority of known toxins indicating that this activity might have been selected rather than more detrimental traits such as DNA-gyrase inhibitors, which are very toxic for cells.