Limitation of phosphate assimilation maintains cytoplasmic magnesium homeostasis

Significance Phosphorus (P) is essential for life. As the fifth-most-abundant element in living cells, P is required for the synthesis of an array of biological molecules including (d)NTPs, nucleic acids, and membranes. Organisms typically acquire environmental P as inorganic phosphate (Pi). While essential for growth and viability, excess intracellular Pi is toxic for both bacteria and eukaryotes. Using the bacterium Salmonella enterica serovar Typhimurium as a model, we establish that Pi cytotoxicity is manifested following its assimilation into adenosine triphosphate (ATP), which acts as a chelating agent for Mg 2+ and other cations. Our findings identify physiological processes disrupted by excessive Pi and how bacteria tune P assimilation to cytoplasmic Mg 2+ levels.