_Toxins_, \(6\), 1002-1020; doi:10.3390/toxins6031002  
_toxins_  
www.mdpi.com/journal/toxins  
_Review_  
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the less stable antitoxin is rapidly degraded and the free active toxin is now capable of targeting essential cellular processes such as DNA replication, cell wall synthesis, cell division or translation, thus leading to growth inhibition and eventually cell death. Growth inhibition by toxins is often reversible when new antiotoxins are available and, accordingly, it has been proposed that activation of TA systems could facilitate bacterial survival until conditions become more favorable [3]. To date, five main types of TA families, with respect to the mode of inhibition of the poisonous activity of the protein toxin, have been described: (_i_) in type I, a small antisense RNA antitoxin specifically inhibits toxin synthesis by interacting with the toxin mRNA; (_ii_) in type II, the antitoxin is a protein that directly binds and inhibits the toxin; (_iii_) in type III the antitoxin is an RNA that directly interacts with the protein toxin; (_iv_) in type IV the antitoxin and the toxin are proteins that have the same target but do not directly interact with each other; and (_v_) in type V the antitoxin is an endoribonuclease, which specifically degrades the toxin mRNA [1, 4, 5]. Although the cellular roles of chromosomally-encoded TA systems are not well established, they have been involved in several processes, including stabilization of genomic regions, anti-addiction against similar plasmid-borne toxins, defense against phage infection, biofilm formation, control of the stress response, and, especially, bacterial persistence [1, 6]. Persister cells are stochastic phenotypic variants of regular cells, which appear randomly and at low frequency in a population and are tolerant to antibiotic treatments due to slow or arrested growth [7]. Remarkably, it was recently shown that stochastic induction of several chromosomal type II TA systems significantly contributes to such persistence phenotype in _E. coli_, thus, indicating a major involvement of TAs in this process [8]. Tuberculosis is the deadliest disease due to a single bacterial pathogen, namely _Mycobacterium tuberculosis_. Besides the synergy with the human immunodeficiency virus (HIV) and the emergence of multi and extensively drug resistant strains, one of the limitations to tuberculosis eradication is its ability to persist in human lungs in a dormant state, which is tolerant to the host immune system and to antibiotic treatments. This phenomenon is thought to be responsible for latent tuberculosis, which affects approximately one third of the human population according to the World Health Organization (WHO), and can reactivate later in case of immune depression. The existence of a persistent subpopulation in the active form of the disease is also believed to be responsible, at least in part, for the exceptionally long duration of the anti-tubercular treatment [9]. _M. tuberculosis_ possesses a remarkably high number of TA systems in its chromosome when compared to other mycobacteria (Figure 1 and Table 1), and it has been proposed that persistence induced by active toxins could contribute to its pathogenesis [10, 11]. Interestingly, a transcriptomic analysis of antibiotic-induced persisters of _M. tuberculosis_ revealed that in addition to a general shutdown of metabolic pathways, at least 10 TA systems were significantly up-regulated under these conditions [12], thus, further supporting a potential contribution of TAs in _M. tuberculosis_ persistence. We have identified a total of 79 TA systems (confirmed or putative) in _M. tuberculosis_ H37 Rv: 67 belonging to six well described type II TA families: VapBC (50 systems), MazEF (10 systems), YefM/YoeB (one system), RelBE (two systems), HigBA (two systems), and ParDE (two systems); one tripartite type II TAC (Toxin-Antitoxin-Chaperone) system controlled by a SecB-like chaperone; three potentially type IV systems; and eight uncharacterized putative TA systems.