Cyclic di-AMP Signaling in Bacteria

Annu Rev Microbiol. 2020 Sep 8:74:159-179. doi: 10.1146/annurev-micro-020518-115943. Epub 2020 Jun 30.


The second messenger molecule cyclic di-AMP (c-di-AMP) is formed by many bacteria and archaea. In many species that produce c-di-AMP, this second messenger is essential for viability on rich medium. Recent research has demonstrated that c-di-AMP binds to a large number of proteins and riboswitches, which are often involved in potassium and osmotic homeostasis. c-di-AMP becomes dispensable if the bacteria are cultivated on minimal media with low concentrations of osmotically active compounds. Thus, the essentiality of c-di-AMP does not result from an interaction with a single essential target but rather from the multilevel control of complex homeostatic processes. This review summarizes current knowledge on the homeostasis of c-di-AMP and its function(s) in the control of cellular processes.

Keywords: Bacillus subtilis; cyclic di-AMP; osmoregulation; potassium transport; second messenger.

Publication types

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

MeSH terms

  • Bacillus subtilis / genetics
  • Bacillus subtilis / metabolism
  • Bacteria / genetics
  • Bacteria / metabolism*
  • Bacterial Proteins / metabolism
  • Cyclic AMP / genetics
  • Cyclic AMP / metabolism*
  • Homeostasis*
  • Riboswitch
  • Second Messenger Systems*
  • Signal Transduction*


  • Bacterial Proteins
  • Riboswitch
  • Cyclic AMP