## 1 Introduction  
Microorganisms need to cope with variations in the external environment and rely on signaling molecules to translate these changes into intracellular responses to mediate adaptation to the new condition. After cells sense an external stimulus (_i.e._, first messenger), a second messenger will be synthesized or degraded to rapidly amplify the first messenger signal and initiate physiological changes. Proteins involved in the synthesis and degradation of second messengers are generally constitutively present in the cell to support rapid activation. First messenger-induced fluctuations of second messengers are propagated in cells through binding to DNA, RNA, or proteins/protein complexes. The ligand-effector complex will then trigger a signal cascade involving specific receptors, outputs and feedback processes. This signal cascade is common for all known second messengers (Figure 1). There is a rich variation of second messengers in prokaryotic organisms, from cyclic nucleotides to gases. In cyanobacteria, the most intensely studied second messengers are calcium (Ca2+), guanosine  
Figure 1: Specific second messengers are regulated by an external stimulus (_i.e._, first messenger) and will bind specific effectors. In turn, the effector will initiate a signal cascade, which leads to organism-specific outputs (examples shown for cyanobacteria). This mechanism is common for all known second messengers. tetraphosphate or pentaphosphate (ppGpp or pppGpp; hereafter (p)ppGpp), and cyclic adenosine 3',5'-monophosphate (cAMP). Lesser-studied second messengers in cyanobacteria are cyclic dimeric GMP (c-di-GMP), cyclic guanosine 3',5'-monophosphate (cGMP) and nitric oxide (NO). By contrast, cyclic dimeric AMP (c-di-AMP) remains to be characterized in cyanobacteria. All of these second messengers are commonly studied in pathogenic bacteria. Calcium has been considered for its ability to influence cell structure and differentiation, motility, and gene expression in pathogenic bacteria [1]. The molecule (p)ppGpp is mainly studied in these bacteria for its involvement under cell starvation stress [2]. Cyclic AMP has been implicated in sugar metabolism [3], motility [4] and virulence [5] in pathogenic bacterial systems. Cyclic di-GMP impacts several processes in bacterial cells including transcription, RNA turnover, biofilm formation, protein synthesis, motility, and virulence [6]. NO serves as an important factor in host-pathogen interactions [7]. Finally, the most recently discovered nucleotide second messengers are c-di-AMP, which affects ion transport, membrane lipid homeostasis, DNA integrity [8], and cGMP, which has been implicated in the control of cyst formation [9]. Cyanobacteria are an ancient and distinct group of gram-negative photoautotrophic bacteria for which there have been limited investigations into the roles of most of these second messengers. Cyanobacteria are one of the most abundant photoautotrophic organisms in oceans [10] and are able to fix both carbon and nitrogen, thereby playing key roles in global carbon and nitrogen cycles. Elucidation of the processes controlling cyanobacterial adaption to aquatic habitats is critical for understanding their roles as primary producers controlling global carbon and nitrogen cycles. Cyanobacteria exhibit extraordinary diversity in terms of genome plasticity, morphological characteristics, ecological niches, and physiological properties [11; 12; 13]. These organisms generally rely on complex signal transduction systems, which reflect their diverse ecophysiological origins and abilities to colonize a wide range of habitats. Cyanobacteria, largely with the exception of marine _Prochlorococcus_ and _Synechococcus_ species, possess a much larger repertoire of two-component proteins compared to other bacteria [14], and they rely heavily on cyclic nucleotide signaling proteins [15; 16; 17]. In recent years, there has been a growing interest in utilizing cyanobacteria as systems for the production of valuable bioindustrial compounds from sugars to biofuels [18; 19].