Mg2+, ATP, and the Control of Bacterial Metabolism

In all living cells, chemical reactions known as metabolism generate energy and building blocks for cellular structures. Metabolism produces and consumes ATP, the major currency of cellular energy. Because approximately 85% of ATP is bound to Mg 2+ , bacteria reduce their ATP concentration when cytoplasmic Mg 2+ availability drops below a certain threshold. This reduction in ATP concentration reshapes metabolism and gene transcription as well as protein synthesis, solubility, and turnover. This article reviews how ATP acts both directly and via ATP-derived signaling molecules, such as 3′,5′-cyclic AMP (cAMP), bis-(3′,5′)-cyclic dimeric-AMP (c-di-AMP), diadenosine tetraphosphate (Ap 4 A), and guanosine-3′,5′-tetra- and pentaphosphate [(p)ppGpp], which direct adaptations to stresses bacteria experience in their natural environments. It also discusses how Mg 2+ -responsive regulatory systems supersede canonical control of metabolism and protein homeostasis by governing ATP amounts and how this bacterial response slows growth, modifies cell envelope structures, and favors survival.