Bacterial Toxin-antitoxin Systems Translation Inhibitors Everywhere the Toxin-antitoxin System Framework the Selfish Nature of Toxin-antitoxin Systems

*Correspondence to: Laurence Van Melderen; Email: [email protected] 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 theymove 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 superfamilies. 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.