## 1 Introduction: A Brief Overview of Toxin-Antitoxin Complexes  
Toxin-antitoxin (TA) systems are compact modules, usually comprising a pair of genes coding for a toxin and a cognate antidote. TA complexes are abundant on plasmids and chromosomes of many bacterial and archaeal species [1; 2; 3; 4; 5; 6]. The toxic components of TA systems can be regarded as intracellular molecular bombs whose release from a complex with their cognate antitoxins triggers bacterial cell death or stasis. In this review we provide current insights into the mechanisms by which expression and activation of these modules are controlled at the transcriptional level which is crucial to understand TA functioning and their possible practical exploitation as emerging targets for novel antibacterial agents. Plasmid encoded TA systems act in postsegregational killing of bacterial cells that have failed to inherit a plasmid during cell division [7]. In progeny deprived of a plasmid, proteolytic degradation of the more labile antitoxin and the lack of its _de novo_ synthesis lead to the release of the stable toxin which interacts with its intracellular target, causing cell death or inhibition of metabolic processes. Thus, bacteria become \"addicted\" to TA modules located on plasmids, as daughter cells die when the plasmid is lost. Chromosomal TAs instead are involved in response to various stress conditions, ensure genomic stability, function as anti-addiction modules, or may act only as selfish genetic entities [3; 8; 9; 10]. TAs also are implicated in antibiotic persistence, biofilm formation, and bacteriophage resistance [11; 12; 13]. TA cassettes currently are classified into five types, based on the characteristics of the antitoxins and the mechanisms by which they counteract the cognate toxins [14; 15]. In a typical type I TA system the toxin is a small hydrophobic protein whereas the antitoxin acts as an antisense RNA which pairs with the toxin mRNA [16; 17]. Inhibition of toxin translation occurs via degradation of RNA duplexes or by masking of the ribosome binding site [18]. In type II modules both toxin and antitoxin are small proteins which form a stable complex. The antitoxin blocks activity of the toxin by hiding the region responsible for toxicity [3]. In type III complexes an antitoxin RNA interacts directly with the toxin protein and in this way abolishes its toxicity [19]. Type IV consists of a protein toxin and a protein antitoxin, the latter preventing toxin to access its target [20; 21]. Finally, type V TAs comprise a protein antitoxin which acts as a ribonuclease that specifically cleaves the toxin mRNA and disables its synthesis [22]. TA systems belonging to the first two types are the most abundant in the prokaryotic world, whereas only single representatives are known to date for the other three classes. This mini review focuses on type II TA modules. The action of a generic type II complex in which both factors are proteins is presented in Figure 1. The toxin and antitoxin factors associate tightly to form the complex. Genes for both proteins are co-expressed from a promoter that is negatively autoregulated by the TA complex. In response to certain environmental conditions, including nutrient limitation or antibiotic exposure, the antitoxin undergoes Clp or Lon protease mediated degradation. The toxin is thereby released and can reach its intracellular target to induce celldormancy, stasis or death [3]. Toxins hinder cellular activities by targeting various structures and key molecular processes [6,14]. Most class II toxins examined to date regulate the translation process by acting as endoribonucleases [23,24]. Some of these endoribonucleases cleave free mRNA in a sequence dependent manner, whereas others target mRNA associated with the ribosomal A site. Certain type II toxins instead inhibit the translation machinery by cleaving initiator tRNA, by phosphorylation of the elongation factor EF-Tu, or by binding to ribosomal subunits [6,25,26,27].