Control of potassium homeostasis is an essential function of the second messenger cyclic di-AMP in Bacillus subtilis

Sci Signal. 2017 Apr 18;10(475):eaal3011. doi: 10.1126/scisignal.aal3011.


The second messenger cyclic di-adenosine monophosphate (c-di-AMP) is essential in the Gram-positive model organism Bacillus subtilis and in related pathogenic bacteria. It controls the activity of the conserved ydaO riboswitch and of several proteins involved in potassium (K+) uptake. We found that the YdaO protein was conserved among several different bacteria and provide evidence that YdaO functions as a K+ transporter. Thus, we renamed the gene and protein KimA (K+ importer A). Reporter activity assays indicated that expression beyond the c-di-AMP-responsive riboswitch of the kimA upstream regulatory region occurred only in bacteria grown in medium containing low K+ concentrations. Furthermore, mass spectrometry analysis indicated that c-di-AMP accumulated in bacteria grown in the presence of high K+ concentrations but not in low concentrations. A bacterial strain lacking all genes encoding c-di-AMP-synthesizing enzymes was viable when grown in medium containing low K+ concentrations, but not at higher K+ concentrations unless it acquired suppressor mutations in the gene encoding the cation exporter NhaK. Thus, our results indicated that the control of potassium homeostasis is an essential function of c-di-AMP.

MeSH terms

  • Bacillus subtilis / genetics
  • Bacillus subtilis / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Dinucleoside Phosphates / genetics
  • Dinucleoside Phosphates / metabolism*
  • Homeostasis / physiology*
  • Potassium / metabolism*
  • Second Messenger Systems / physiology*


  • Bacterial Proteins
  • Dinucleoside Phosphates
  • cyclic diadenosine phosphate
  • Potassium