Cyclic di-AMP: another second messenger enters the fray

Nat Rev Microbiol. 2013 Aug;11(8):513-24. doi: 10.1038/nrmicro3069. Epub 2013 Jul 1.


Nucleotide signalling molecules contribute to the regulation of cellular pathways in all forms of life. In recent years, the discovery of new signalling molecules in bacteria and archaea, as well as the elucidation of the pathways they regulate, has brought insights into signalling mechanisms not only in bacterial and archaeal cells but also in eukaryotic host cells. Here, we provide an overview of the synthesis and regulation of cyclic di-AMP (c-di-AMP), one of the latest cyclic nucleotide second messengers to be discovered in bacteria. We also discuss the currently known receptor proteins and pathways that are directly or indirectly controlled by c-di-AMP, the domain structure of the enzymes involved in its production and degradation, and the recognition of c-di-AMP by the eukaryotic host.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bacteria / genetics
  • Bacteria / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Wall / genetics
  • Cell Wall / metabolism
  • Dinucleoside Phosphates / genetics
  • Dinucleoside Phosphates / metabolism*
  • Eukaryotic Cells / metabolism
  • Eukaryotic Cells / microbiology
  • Gene Expression Regulation, Bacterial*
  • Host-Pathogen Interactions
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Phosphorus-Oxygen Lyases / classification
  • Phosphorus-Oxygen Lyases / genetics
  • Phosphorus-Oxygen Lyases / metabolism*
  • Protein Structure, Tertiary
  • Protein Transport
  • Proteolysis
  • Signal Transduction*
  • Transcription, Genetic


  • Carrier Proteins
  • Dinucleoside Phosphates
  • Intracellular Signaling Peptides and Proteins
  • cyclic GMP-binding protein
  • cyclic diadenosine phosphate
  • Phosphorus-Oxygen Lyases
  • diadenylate cyclase, Bacillus subtilis