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.