Department of Pathology and Laboratory Medicine, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
The One Health Microbiome Center, Huck Institute of the Life Sciences, Pennsylvania State University, Camp Hill, Pennsylvania, USA.
mBio. 2024 Sep 11;15(9):e0164224. doi: 10.1128/mbio.01642-24. Epub 2024 Aug 6.
Bacteria acquire P primarily as inorganic orthophosphate (Pi, PO). Once internalized, Pi is rapidly assimilated into biomass during the synthesis of ATP. Because Pi is essential, but excessive ATP is toxic, the acquisition of environmental Pi is tightly regulated. In the bacterium (), growth in Pi-limiting environments activates the membrane sensor histidine kinase PhoR, leading to the phosphorylation of its cognate transcriptional regulator PhoB and subsequent transcription of genes involved in adaptations to low Pi. Pi limitation promotes PhoR kinase activity by altering the conformation of a membrane signaling complex comprised of PhoR, the multicomponent Pi transporter system PstSACB and the regulatory protein PhoU. However, the identity of the Pi-starvation signal and how it controls PhoR activity remain unknown. Here, we identify conditions where the PhoB and PhoR signal transduction proteins can be maintained in an inactive state when is grown in media lacking Pi. Our results demonstrate that PhoB/PhoR is activated by an intracellular P-insufficiency signal.IMPORTANCEIn enteric bacteria, the transcriptional response to phosphorus (P) starvation is controlled by a specialized signal transduction system comprised of a membrane-bound, multicomponent signal sensor, and a cytoplasmic transcriptional factor. Whereas this system has been primarily studied in the context of phosphate (Pi) starvation, it is currently unknown how this stress initiates signal transduction. In the current study, we establish that this signaling system is regulated by a cytoplasmic signal arising from insufficient P. We demonstrate that rather than responding to extracellular conditions, cells couple the activation of their P starvation response to the availability of cytoplasmic P. This regulatory logic may enable cells to prevent toxicity resulting from excessive Pi acquisition and hinder the onset of a P starvation response when their metabolic demands are being met through the consumption of P sources other than Pi.
细菌主要通过无机正磷酸盐（Pi，PO ）获得 P。一旦内化，Pi 就在合成 ATP 的过程中迅速被同化到生物量中。因为 Pi 是必需的，但过量的 ATP 是有毒的，所以环境 Pi 的获取受到严格调控。在细菌 （）中，在 Pi 限制环境中生长会激活膜传感器组氨酸激酶 PhoR，导致其同源转录调节剂 PhoB 磷酸化，并随后转录参与适应低 Pi 的基因。Pi 限制通过改变由 PhoR、多组分 Pi 转运系统 PstSACB 和调节蛋白 PhoU 组成的膜信号复合物的构象来促进 PhoR 激酶活性。然而，Pi 饥饿信号的身份以及它如何控制 PhoR 活性仍然未知。在这里，我们确定了在缺乏 Pi 的培养基中生长时可以将 PhoB 和 PhoR 信号转导蛋白保持在非活性状态的条件。我们的结果表明，PhoB/PhoR 被细胞内 P 不足信号激活。
在肠细菌中，对磷（P）饥饿的转录反应由一个由膜结合的多组分信号传感器和一个细胞质转录因子组成的专门信号转导系统控制。虽然这个系统主要在磷酸盐（Pi）饥饿的背景下进行研究，但目前还不清楚这种应激如何引发信号转导。在当前的研究中，我们确定这个信号系统受到细胞质信号的调节，该信号源于 P 不足。我们证明，细胞不是对细胞外条件做出反应，而是将其 P 饥饿反应的激活与细胞质 P 的可用性联系起来。这种调节逻辑可能使细胞能够防止因过度获取 Pi 而导致的毒性，并防止在其代谢需求通过消耗除 Pi 以外的 P 源来满足时发生 P 饥饿反应。
