Essentiality of c-di-AMP in Bacillus subtilis: Bypassing mutations converge in potassium and glutamate homeostasis

In order to adjust changing environmental conditions, bacteria use nucleotide second messengers transduce external signals and translate them into a specific cellular response. Cyclic di-adenosine monophosphate (c-di-AMP) is the only known essential messenger. addition well-established role of this messenger in control potassium homeostasis, we observed that glutamate as toxic for c-di-AMP-free strain Gram-positive model bacterium Bacillus subtilis . work, isolated suppressor mutants allow growth under these conditions. Characterization resistant suppressors revealed they contain pairs mutations, most cases affecting homeostasis. Among several independent mutations affected novel transporter, AimA ( A mino acid im porter , formerly YbeC). This protein major transporter serine B Unexpectedly, some could suppress toxicity by combination affect phospholipid biosynthesis gain-of-function mutation mechanosensitive channel small conductance (YfkC) resulting acquisition device export. Cultivation on complex medium was an even greater challenge because amounts potassium, glutamate, other osmolytes are substantially higher than minimal medium. Suppressor viable be anaerobic conditions if one two c-di-AMP receptor proteins, DarA or DarB, absent. Also medium, osmolyte bottlenecks absence c-di-AMP. Our results indicate essentiality caused global impact different aspects physiology.