Bruna Roberto E, Kendra Christopher G, Groisman Eduardo A, Pontes Mauricio H
Department of Pathology and Laboratory Medicine, Pennsylvania State College of Medicine, Hershey, PA 17033.
Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06536.
Proc Natl Acad Sci U S A. 2021 Mar 16;118(11). doi: 10.1073/pnas.2021370118.
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 Mg-dependent processes that result, in part, from Mg chelation by ATP. We establish that the MgtC protein inhibits uptake of the ATP precursor Pi when serovar Typhimurium experiences cytoplasmic Mg 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 is not limiting, excessive Pi uptake increases ATP synthesis, depletes free cytoplasmic Mg, inhibits protein synthesis, and hinders growth. Our results provide a framework to understand the molecular basis for Pi toxicity. Furthermore, they suggest a regulatory logic that governs P assimilation based on its intimate connection to cytoplasmic Mg homeostasis.
磷（P）是核心生物分子的重要组成部分。在细菌中，磷主要以无机正磷酸盐（Pi）的形式获取，并在细胞质中被同化为三磷酸腺苷（ATP）。尽管磷是必不可少的，但细胞质中过量的Pi会阻碍生长。我们现在报告，细菌会限制Pi的摄取，以避免破坏依赖镁的过程，这些过程部分是由ATP与镁螯合导致的。我们确定，当鼠伤寒血清型沙门氏菌经历细胞质镁饥饿时，MgtC蛋白会抑制ATP前体Pi的摄取。这种反应可防止ATP积累和核糖体RNA的过量产生，而这两者最终共同阻碍细菌生长并导致活力丧失。即使细胞质中的镁不缺乏，过量摄取Pi也会增加ATP合成，耗尽细胞质中的游离镁，抑制蛋白质合成，并阻碍生长。我们的结果提供了一个框架，以理解Pi毒性的分子基础。此外，它们还提出了一种基于磷与细胞质镁稳态的密切联系来控制磷同化的调节逻辑。
