Research ArticleMicrobiology

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

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Science Signaling  18 Apr 2017:
Vol. 10, Issue 475, eaal3011
DOI: 10.1126/scisignal.aal3011

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c-di-AMP controls potassium homeostasis in bacteria

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.

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