TY - JOUR T1 - A rendezvous of two second messengers: The c-di-AMP receptor protein DarB controls (p)ppGpp synthesis in <em>Bacillus subtilis</em> JF - bioRxiv DO - 10.1101/2020.08.27.268672 SP - 2020.08.27.268672 AU - Larissa Krüger AU - Christina Herzberg AU - Dennis Wicke AU - Heike Bähre AU - Jana L. Heidemann AU - Achim Dickmanns AU - Kerstin Schmitt AU - Ralf Ficner AU - Jörg Stülke Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/08/27/2020.08.27.268672.abstract N2 - Many bacteria use cyclic di-AMP as a second messenger to control potassium and osmotic homeostasis. In Bacillus subtilis, several c-di-AMP binding proteins and RNA molecules have been identified. Most of these targets play a role in controlling potassium uptake and export. In addition, c-di-AMP binds to two conserved target proteins of unknown function, DarA and DarB, that exclusively consist of the c-di-AMP binding domain. Most likely these proteins transduce their signal by regulatory interactions with other proteins. Here, we have investigated the function of the c-di-AMP-binding protein DarB in B. subtilis, a protein consisting of two CBS (cystathionine-beta synthase) domains. We have used an unbiased search for DarB interaction partners and identified the (p)ppGpp synthetase/hydrolase Rel as a major interaction partner of DarB. (p)ppGpp is another second messenger that is formed upon amino acid starvation and under other stress conditions to stop translation and active metabolism. The interaction between DarB and Rel only takes place if the bacteria grow at very low potassium concentrations and intracellular levels of c-di-AMP are low. Indeed, c-di-AMP inhibits the binding of DarB to Rel. The interaction results in the Rel-dependent accumulation of pppGpp. Our results link potassium and c-di-AMP signaling to the stringent response and thus to the global control of cellular physiology.Competing Interest StatementThe authors have declared no competing interest. ER -