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

The second messenger cyclic di-adenosine monophosphate (c-di-AMP) is essential in the Gram-positive model organism and in related pathogenic bacteria. It controls the activity of the conserved 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 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.