Cyclic di-AMP (also called c-di-AMP and c-di-adenosine monophosphate) is a second messenger used in signal transduction in bacteria and archaea.
In bacteria, cyclic di-AMP has been implicated in the control of growth, cell wall homeostasis, bacterial biofilm formation and virulence gene expression, heat and osmotic stress regulation and responses, sporulation, potassium transport, lysis, and antibiotic resistance.
Synthesis is regulated a number of ways, including negative feedback inhibition and upregulation through a decrease in phosphodiesterase.
[9] At high concentrations, cyclic di-AMP binds to receptor and target proteins to control specific pathways.
Elevated c-di-AMP levels have also been linked to increased resistance toward cell wall-damaging antibiotics (e.g. β-lactams) and reduced cellular turgor.
[12][13] Cyclic di-AMP has been linked to fatty acid synthesis regulation in Mycobacterium smegmatis, the growth of S. aureus in conditions of low potassium, the sensing of DNA integrity in B. subtilis, and cell wall homeostasis in multiple species.
[19] In eukaryotic cells, c-di-AMP is sensed and subsequently elicits a type I interferon (IFN) response, leading to the activation of defense mechanisms against viral infection.
[22] c-di-AMP activates the innate immune pathway STING (stimulator of interferon genes) to detect damaged DNA.