## 1 Introduction  
Bacteria use several different nucleotide-derived molecules as second messengers for the control of important cellular functions [1]. Of these, 3\({}^{\prime}\),5\({}^{\prime}\)-cyclic diadenosine monophosphate (c-di-AMP) has an outstanding role as it is the only known nucleotide second messenger, which seems to be essential for bacterial survival, at least under most standard laboratory conditions [2, 3, 4, 5]. In Firmicutes, such as _Bacillus subtilis_, _Staphylococcus aureus_ and _Listeria monocytogenes_, where c-di-AMP has mostly been studied, this molecule fulfils a major role in the control of ion homeostasis, but its implication in cell wall synthesis, DNA integrity and sporulation has also been shown [5, 6, 7, 8, 9, 10]. Furthermore, c-di-AMP is also involved in virulence and host interactions in pathogens, such as _Listeria_ and _Chlamydia_[11, 12, 13]. C-di-AMP has been first detected during the structural investigation of the DNA integrity scanning protein A (DisA) of _Thermotoga maritima_ and _B. subtilis_[14]. The homo-octameric enzymes synthesize c-di-AMP by joining two adenosine triphosphate (ATP) molecules via phosphodiester linkages and have been described as migrating along DNA, where they interact with stalled replication forks and Holliday junctions in _B. subtilis_[14, 15]. Up to now, different types of such diadenylate cylases (DACs) have been identified, which all contain the so-called 'DAC domain' [16]. As DisA, the two other important types of DACs were also discovered in _B. subtilis_: The membrane-bound CdaA, which seems to be linked to potassium/ion homeostasis, and the small soluble CdaS involved in sporulation processes [4; 17]. In contrast to _B. subtilis_, other organisms often possess only one DAC. For example, Firmicutes, such as _L. monocytogenes_ or _S. aureus_, contain only a CdaA homolog, whereas Actinobacteria seem to be limited to DisA homologs [16; 18]. However, DAC-encoding genes (and thus c-di-AMP signaling mechanisms in general) are widely spread, mostly represented in Gram-positive bacteria, but they are also found in Gram-negatives, such as Cyanobacteria and Chlamydia, and even in the kingdom of archaea [19]. In contrast to DACs, the phosphodiesterase (PDEs) involved in c-di-AMP degradation instead show more structural diversity [16]. Here, two-step degradation via the linear intermediate 5'-phosphoadenylly-(3'\(\rightarrow\)5')-adenosine (pApA) and one-step mechanisms via direct hydrolysis of two molecules of AMP have been described [20; 21]. In contrast to DAC activity, c-di-AMP cleavage cannot be attributed to one particular domain, but instead it is mediated by various completely different structures [16]. Although several enzymes share similarities in domain architecture, such as the well-characterized DhhP-type PDEs first described in _Borrelia burgdorferi_[22; 23], others appear significantly different, such as the recently discovered AtaC from _Streptomyces Venezuela_, which does not contain any of the domains described to be involved in c-di-AMP hydrolysis previously [24]. The mechanisms by which c-di-AMP regulates cellular processes include protein interaction, e.g., as ligands of transcriptional regulators, such as BusR of _Lactococcus lactis_, or with regulatory domains of enzymes, e.g., the potassium transporter KtrA in _S. aureus_[7; 25]. In addition, it was also described to act as an effector molecule of c-di-AMP-specific riboswitches [26]. The first described member of these c-di-AMP riboswitches is located in the 5' untranslated region (UTR) of the _ydaO_ gene in _B. subtilis_, which encodes for the potassium importer KimA [4; 26]. Upon the binding of c-di-AMP, the formation of a terminator stem loop occurs, which then results in premature transcription termination [26; 27]. Thus, c-di-AMP riboswitches are considered to act as so-called 'off'-switches [26].