## 1 Introduction  
Folic acid (vitamin B9) plays a pivotal role in both prokaryotic and eukaryotic cells for the biosynthesis of many cellular components [1]. Humans cannot synthesize folates and so depend on an exogenous supply, whereas most prokaryotes synthesize this essential cofactor _de novo_[2] which makes the folate metabolic pathway an interesting target in urinary tract infections [3], chemotherapy, and malarial disease treatment [4]. The reduced form of folic acid, tetrahydrofolate (THF) serves as the donor of one-carbon units in myriad metabolic pathways involved in the formation of purines, thymidine, glycine, and methionine [5]. THF is also required for synthesizing formylmethionyl-tRNA(tm) which is essential for initiation of protein synthesis in bacteria [6]. Depletion of the intracellular THF pool causes \"thymineless death\" in rich medium where bacteria undergo cell-death due to thymine starvation or leads to a stringent response in minimal medium where the bacterial population enters a non-dividing state due to amino acid starvation [5]. The stringent response involves accumulation of the regulatory alarmone guanosine triphosphate (ppGpp) [7]. One of the ways to cope with nutritional stress for bacteria is activation of toxin-antitoxin (TA) systems through ppGpp to achieve a non-metabolizing dormancy state [8,9]. This quiescent state is called \"persistence\" in which bacterial cells are tolerant to antibiotics. TA systems are diverse and abundant in free-living prokaryotes [10]. A TA system usually consists of two genes in an operon that encode for a stable toxin that damages the bacterial cell that makes the toxin (rather than affecting another cell) by inhibiting a critical physiological step and a labile antitoxin, which protects the host by blocking the deleterious activity of the toxin [11]. The cellular targets of these toxins are quite diverse including DNA replication machinery, mRNA, protein synthesis, cell membranes, ATP synthesis [12], and DNA [13]. To date, five types of TA systems have been categorized depending on the role of the antiotoxins. In type I systems, antitoxin RNA silences the toxin by binding to the toxin mRNA [14], and in type III systems, the antitoxin RNA binds to the toxin via its organized repeat motifs [15]. In type II, IV, and V systems, the protein antitoxin either directly binds the toxin (type II) [16], interferes with the binding of the toxin to its target (type IV) [17], or degrades the toxin mRNA via its specific enzymatic endoribonuclease activity (type V) [18]. The recently characterized type V TA system comprises of a membrane lytic toxin, GhoT and an unique antitoxin, GhoS which is not labile during stress and does not participate in transcriptional control of the TA pair; rather, it functions as an antitoxin by specifically cleaving _ghoT_ mRNA. Although initially discovered related to plasmid maintenance [19], their ubiquitousness in bacterial chromosomes have made TA loci the subject of intense scrutiny to unveil their enigmatic role in cell physiology. In most cases, deletion of a single TA pair rarely has any impact on cell physiology [20] and ectopic expression of toxins is often required to study their effect on bacterial growth. For example, persistence was unchanged with deletion of single toxin genes even with severe antibiotic stress [21] whereas successive deletion of 10 type II TA systems led to reduced persistence level [20]. Despite these difficulties in determining physiological roles, TA systems are clearly phage inhibition systems [15; 22; 23] and stress-response elements [24; 25]. There is also increasing evidence supporting the role of TA systems in achieving bacterial persistence [26; 27; 28]. For instance, deletion of type II toxin gene _mqsR_ and the TA locus _mqsRA_ both reduced persistence level [27]. Supporting this result, type I toxin TisB was directly linked with persistence as absence of _tisAB/istR_ locus led to significant reduction in ciprofloxacin induced persistence [28].