Cyclic di-AMP: Small molecule with big roles in bacteria

Cyclic dinucleotides are second messengers that are present in all the three domains of life, bacteria, archaea, and eukaryotes. These dinucleotides have important physiological and pathophysiological roles in bacteria. Cyclic di-AMP (cdA) is one of the recently discovered cyclic dinucleotides present predominantly in gram-positive bacteria. cdA is synthesized through diadenylate cyclase (DAC) activity from ATP in a two-step process and hydrolyzed to linear dinucleotide pApA (and to 5’ AMP in certain cases) by specific phosphodiesterases. cdA regulates various physiological processes like K+ transport and osmotic balance, DNA repair, cell wall homeostasis, drug resistance, central metabolism either by binding directly to the target protein or regulating its expression. It also participates in host-pathogen interaction by binding to host immune receptors ERAdP, RECON, and STING. •Cyclic di-AMP (cdA) is a secondary messenger present predominantly in gram positive bacteria.•cdA is synthesized from ATP in a two-step process through diadenylate cyclase reaction.•It is hydrolyzed by specific phosphodiesterases.•cdA regulates bacterial K+ and osmolyte transport, cell wall homeostasis, central metabolic pathways and DNA damage repair.•cdA regulates the expression of RecA as well as its DNA strand exchange activity in Mycobacterium.•It can regulate the different pathways by binding to the target proteins or the RNAs.•It also induces type I INF response in mammalian host.