## 1 Introduction  
The toxin-antitoxin (TA) system-related research is an evolving field. Most of the TA modules in bacteria were discovered during the first decade of the current millennium, and studies have indicated that TA genes are encoded on plasmids and/or chromosomes of almost all bacteria and many archaea [1; 2]. The significance of the TA system lies in regulating cell growth and death to help prokaryotes cope with different stress conditions [2]. The TA system is composed of a stable toxin protein and a cognate labile antitoxin that is either a protein or an RNA neutralizing the toxin [3]. There are six types of TA systems that differ in terms of the antitoxin nature and the mechanism of neutralizing the toxin [3]. Type I and II are the most abundant in prokaryotes. Type II has been widely studied [1], but it has not been well-studied in thermophilic bacteria, including _Geobacillus_ (see below). In the type II TA system, the antitoxin is a protein that forms a stable complex with the toxin to neutralize it and block its toxic activity under normal growth conditions [2; 4]. Under stress conditions, the antitoxin is degraded by a protease, releasing the stable toxin to interact with its cellular target and influence a cellular process that could have a bacteriostatic or a bactericidal effect [1; 5]. Even membersof the same toxin protein superfamily differ significantly in their amino acid (aa) sequences, and thus have different interactions with different cellular targets [6]. TA-coding genes are often found in an operon and are thus co-regulated [7]; however, this is not necessarily the case all the time, as explained in the Results and Discussion section. TA-coding genes may overlap [8], and the antitoxin-coding gene is often located upstream of the toxin-coding gene. This order guarantees synthesis of the antitoxin before that of the toxin [2]. However, exceptions have been reported [2]. TAs can be present as one pair or more per cell [5]. The plasmid-encoded TA loci are often associated with plasmid stabilization via a mechanism known as post-segregational killing (PSK) [1]. While there is evidence that some chromosomally encoded TA pairs are involved in genome stability via the PSK mechanism as well [1; 3; 5], such as the case with the RelBE TA family of _E. coli_-K12 [9] and ParDE in _Vibrio_ spp. [10; 11], the roles for many are varied and still debated [8]. Chromosomally encoded TA pairs may be involved in responses of bacterial cells to various stress conditions [1; 3; 8], including nutrient deficiency and bacteriophage infection, as shown for the _E. coli_ MazEF TA family [12; 13], and exposure to antibiotics and formation of persisters, as shown for various type II TA families of the pathogenic _Salmonella_ spp. [14]. They may also be involved in bacterial programmed cell death (PCD), which can be described as an altruistic suicide, a role that was described for the MazEF TA family in different _E. coli_ strains [15; 16] but has been opposed [17], and may as well be involved in biofilm formation [1; 5], such as the case with the MqsRA TA family in different _E. coli_ strains [18]. Furthermore, TAs may help bacteria in colonizing niches [3; 5], such as the case with the PasTI TA family of the pathogenic _E. coli_ ExPEC strain [19], and play a role in virulence in pathogenic bacteria [5; 8], such as the case with the PezAT TA family of _Streptococcus pueumoniae_[20] and SezAT TA family of _Streptococcus suis_[21]. Regulation of the TA modules is connected to cellular signaling pathways [3]. Cell signaling molecules, such as the (p)ppGpp (guanosine tetra or pentaphosphate, known as the alarmones [22], play a vital role in the regulation of the transcription and translation of TA modules, and thus bacterial physiology [3]. The (p)ppGpp is a global regulatory signal in bacteria, induced by nutrient-starvation and, in turn, activates the toxin by activating proteases that degrade the antitoxin [3; 23] (the (p)ppGpp role is discussed further in Section 2.8.1).