coli_ sequence-specific endoribonuclease MazF induces a growth arrest _via_ cleavage of almost all cellular mRNAs in a ribosome-independent manner [32]. The _E. coli_ MazEF complex in which the toxin MazF is inactive forms a linear heterohexamer composed of a dimer of the MazE antitoxin symmetrically bound to two MazF dimers [33]. Similar organization and stoichiometry is observed for the MazEF complex of _Bacillus subtilis_, although the MazE antitoxins are poorly related and present different fold [34]. Several MazF cleavage sites in mRNA have been reported, for example MazF from _E. coli_ cleaves at ACA sequences [35] and the one from _B. subtilis_ at UACAU [36]. Out of the 10 MazF toxin members present in _M. tuberculosis_, seven were shown to affect _E. coli_ and/or _M. smegmatis_ growth, two exhibited non-noticeable phenotype, and one has not been tested (Figure 1. [15, 16, 37]. Analysis of cleavage sites in mRNA, which has been performed for several MazF toxins of _M. tuberculosis_ revealed significant differences. Indeed, while MazF9 cleaves at UAC sequences, MazF3 cleaves U rich regions [37], MazF6 at UUCCU sequences [37, 38], and MazF4 at UCGCU [39]. Such differences in substrate recognition suggest that MazF toxins may trigger a large panel of responses, going from a global translation inhibition to a fine-tuned regulation of specific mRNAs. For example, in the case of MazF6, 31% of the total mRNA do not present the recognition site and are, thus, predicted to be resistant to toxin cleavage. In addition to mRNA recognition, certain MazF toxins were shown to target ribosomal RNA. It is indeed the case for the _E. coli_ MazF toxin, which generates specialized ribosomes by cleavage of the 3' region of the 16S rRNA containing the anti-Shine-Dalgarno sequence, thus, facilitating leaderless mRNAs translation [40]. This mechanism would lead to an alternative translation pathway, which might promote stress adaptation. The MazF6 toxin from _M. tuberculosis_ also acts on ribosomal RNA but by a very distinct mechanism. In this case, the toxin cleaves the 23S rRNA of dissociated ribosomes and subsequently provokes a global inhibition of protein synthesis [38]. Aside from RNA targets, it has been shown that the mycobacterial MazF4 toxin interacts with DNA topoisomerase I and that they mutually inhibit each other [17]. As the DNA topoisomerase I gene is essential in _M. tuberculosis_[41], this suggests that MazF4 could act by two alternative mechanisms to inhibit bacterial growth. Expression of _mazEF_ from _E. coli_ is induced under various stress conditions, including DNA damage, heat shock and oxidative stress in a RelA dependent manner [42]. Similarly, it has been shown that _M. tuberculosis_ MazF2 was down-regulated after four hours of nutrient starvation and MazF3 up-regulated during amino acid starvation in a _relA_ deleted strain [43, 44], thus, suggesting that MazEF modules from _M. tuberculosis_ could also be regulated by the stringent response. As observed for RelE toxins (see next part), overexpression of either MazF1 (Rv2801c), MazF5 (Rv1942c), or MazF6 (Rv1102c) from _M. tuberculosis_ induced drug-specific effects on the formation of persister cells (data not shown from [18]). Correspondingly, individual deletion of each of these three MazF encoding genes from _M. tuberculosis_ differentially diminished the formation of drug-tolerant persisters [18]. Although not yet studied in detail, these data point towards an implication of MazEF modules in the formation of _M. tuberculosis_ persisters in response to antibiotic treatment. Partner specificity among TA pairs in _M. tuberculosis_ has been studied as well. The presence of 79 possible TAs in this bacterium represents a unique system to address possible cross-talks, overlaps, or cooperation between TA systems. Remarkably, the _M. tuberculosis_ MazF9 toxin was shown to be neutralized by the non-cognate antiotoxins MazE6, VapB27, and VapB40 [19].