Cyclic nucleotides in archaea: Cyclic di‐AMP in the archaeon Haloferax volcanii and its putative role

The role of cyclic nucleotides as second messengers for intracellular signal transduction has been well described in bacteria. One recently discovered bacterial second messenger is cyclic di‐adenylate monophosphate (c‐di‐AMP), which has been demonstrated to be essential in bacteria. Compared to bacteria, significantly less is known about second messengers in archaea. This study presents the first evidence of in vivo presence of c‐di‐AMP in an archaeon. The model organism Haloferax volcanii was demonstrated to produce c‐di‐AMP. Its genome encodes one diadenylate cyclase (DacZ) which was shown to produce c‐di‐AMP in vitro. Similar to bacteria, the dacZ gene is essential and homologous overexpression of DacZ leads to cell death, suggesting the need for tight regulation of c‐di‐AMP levels. Such tight regulation often indicates the control of important regulatory processes. A central target of c‐di‐AMP signaling in bacteria is cellular osmohomeostasis. The results presented here suggest a comparable function in H. volcanii. A strain with decreased c‐di‐AMP levels exhibited an increased cell area in hypo‐salt medium, implying impaired osmoregulation. In summary, this study expands the field of research on c‐di‐AMP and its physiological function to archaea and indicates that osmoregulation is likely to be a common function of c‐di‐AMP in bacteria and archaea.