PT - JOURNAL ARTICLE AU - Gundlach, Jan AU - Herzberg, Christina AU - Kaever, Volkhard AU - Gunka, Katrin AU - Hoffmann, Tamara AU - Weiß, Martin AU - Gibhardt, Johannes AU - Thürmer, Andrea AU - Hertel, Dietrich AU - Daniel, Rolf AU - Bremer, Erhard AU - Commichau, Fabian M. AU - Stülke, Jörg TI - Control of potassium homeostasis is an essential function of the second messenger cyclic di-AMP in <em>Bacillus subtilis</em> AID - 10.1126/scisignal.aal3011 DP - 2017 Apr 18 TA - Science Signaling PG - eaal3011 VI - 10 IP - 475 4099 - http://stke.sciencemag.org/content/10/475/eaal3011.short 4100 - http://stke.sciencemag.org/content/10/475/eaal3011.full SO - Sci. Signal.2017 Apr 18; 10 AB - In Bacillus subtilis, the second messenger cyclic di-AMP (c-di-AMP) regulates the expression of many genes encoding potassium transporters by binding to a regulatory RNA structure called a riboswitch in a gene called ydaO, preventing transcription beyond the riboswitch. Gundlach et al. found that ydaO encoded a high-affinity potassium transporter and renamed it kimA (K+ importer A). Binding of c-di-AMP to the kimA riboswitch under high external concentrations of potassium and the resulting inhibition of kimA expression were essential to ensure bacterial viability under these conditions. KimA is a member of an evolutionarily conserved family of potassium transporters, suggesting that this regulatory mechanism for potassium homeostasis could be widespread among diverse bacterial taxa.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.