biostudies-literatureBruna RENIAID NIH HHSHHS | NIH | National Institute of Allergy and Infectious Diseasese2021370118https://www.ebi.ac.uk/biostudies/studies/S-EPMC7980370biostudies-literatureUnknown118(11)Phosphorus (P) is an essential component of core biological molecules. In bacteria, P is acquired mainly as inorganic orthophosphate (Pi) and assimilated into adenosine triphosphate (ATP) in the cytoplasm. Although P is essential, excess cytosolic Pi hinders growth. We now report that bacteria limit Pi uptake to avoid disruption of Mg²⁺-dependent processes that result, in part, from Mg²⁺ chelation by ATP. We establish that the MgtC protein inhibits uptake of the ATP precursor Pi when <i>Salmonella enterica</i> serovar Typhimurium experiences cytoplasmic Mg²⁺ starvation. This response prevents ATP accumulation and overproduction of ribosomal RNA that together ultimately hinder bacterial growth and result in loss of viability. Even when cytoplasmic Mg<sup>2+<Proceedings of the National Academy of Sciences of the United States of AmericaLimitation of phosphate assimilation maintains cytoplasmic magnesium homeostasis.PMC7980370AI148774R21 AI148774R01 AI049561Pontes MHKendra CGBruna REGroisman EAfalseLimitation of phosphate assimilation maintains cytoplasmic magnesium homeostasis.Phosphorus (P) is an essential component of core biological molecules. In bacteria, P is acquired mainly as inorganic orthophosphate (Pi) and assimilated into adenosine triphosphate (ATP) in the cytoplasm. Although P is essential, excess cytosolic Pi hinders growth. We now report that bacteria limit Pi uptake to avoid disruption of Mg²⁺-dependent processes that result, in part, from Mg²⁺ chelation by ATP. We establish that the MgtC protein inhibits uptake of the ATP precursor Pi when <i>Salmonella enterica</i> serovar Typhimurium experiences cytoplasmic Mg²⁺ starvation. This response prevents ATP accumulation and overproduction of ribosomal RNA that together ultimately hinder bacterial growth and result in loss of viability. Even when cytoplasmic Mg<sup>2+<2021-01-01T00:00:00Z2021 Mar2025-04-04T22:01:03.946Z2025-04-04T22:01:03.946ZS-EPMC79803703370721010.1073/pnas.2021370118