# Toxin-Antitoxin Systems in Pathogenic Bacteria
###### Abstract  
Toxin-antitoxin systems in Pathogenic Bacteria, _Toxins_ **2021**, 13, 74. [[https://doi.org/10.3390/toxins13020074](https://doi.org/10.3390/toxins13020074)]([https://doi.org/10.3390/toxins13020074](https://doi.org/10.3390/toxins13020074))  
Footnote †: journal: Physics Letters B  
pursued. The [PERSON] et al. paper examined the expression of the _mbcAT_ operon and its regulation [10]. The _Mycobacterium tuberculosis_ type II MbcT toxin halts cell proliferation through the phosphorylosis of the essential metabolite NAD\({}^{+}\), and its effect is neutralized by physical interaction with its cognate antitoxin MbcA. The authors developed a dual fluorescent reporter system, which was used to dissect the operon promoter/operator region at the genetic level. Using this system, it was demonstrated that transcription from the _PmbcA_ promoter is induced by a range of stress conditions, reflecting those encountered inside the infected host and uncovering that this TA system could be exploited to treat tuberculosis [10].  
Two papers within this Special Issue are focused on different aspects of toxins of the MazF/PemK superfamily that cleaves mRNA in a sequence-specific and ribosome-independent manner [11; 12]. [PERSON] et al. conducted an in-depth structural and functional analysis on the mRNA interfares (RNase) of the MazF/PemK family in _Bacillus cereus_[11]. [PERSON] et al. studied the molecular mechanisms associated with chlorhexidine (CHLX) adaptation in two clinical strains of _Klebsiella pneumoniae_ by phenotypic and transcriptomic analyses and their association with a new PemK/PemI TA system [12]. [PERSON] et al. have found by bioinformatic analysis 49 putative TA systems in _Stentotrophomonas maltophilia_, and asked whether clinical and environmental isolates contain a different set of type II TA systems [13]. The authors observed that RelBE, HicAB, and the previously undescribed COG3832-ArsR operon were present solely in clinical _S. maltophilia_ isolates collected in Lithuania, while HipBA was more frequent in the environmental ones. The paper by [PERSON] et al. explores toxin \(\zeta\), which reduces the ATP and GTP levels, increases the (p)ppGpp and c-di-AMP pool and inactivates a fraction of uridine diphosphate-N-acetylglucosamine (UNAG), transiently inducing reversible dormancy. The authors, using a genetic orthogonal control of toxin \(\zeta\) and antitoxin \(\varepsilon\) levels in _B. subtilis_ cells, have shown that transient toxin \(\zeta\) expression causes a metabolic heterogeneity that induces toxin and Amp dormancy over a long window of time rather than cell persistence. Antitoxin \(\varepsilon\) expression, by reversing \(\zeta\) activities, facilitates the exit of Amp-induced dormancy both in _rec\({}^{+}\)_ and _recA_ cells. It has been proposed that an unexploited target to fight against antibiotic persistence is to disrupt toxin-antitoxin interactions [14]. Lastly, the paper by [PERSON] et al. examined how the TA systems could be developed as targets for novel antimicrobials, and discussed possible undesirable effects of such therapeutic intervention, such as the induction of persister cells, biofilm formation and toxicity in eukaryotic cells [15].  
Our laboratory was funded by Ministerio de Ciencia e Innovacion/Agencia Estatal de Investigacion (MCI/AEI)/FEDER, EU, grant number PGC2018-097054-B-I00.  
The editor is grateful to all the authors who contributed their work and to the expert peer reviewers that contribute with their rigorous evaluations of all the manuscripts submitted to this Special Issue. The valuable contribution, organization, and editorial support of the MDPI management team and staff is greatly acknowledged.  
The author declares no conflict of interest.