Department of Microbiology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Microbiology (Reading). 2022 Apr;168(4). doi: 10.1099/mic.0.001185.
Inorganic polyphosphate (polyP) is synthesized by bacteria under stressful environmental conditions and acts by a variety of mechanisms to promote cell survival. While the kinase that synthesizes polyP (PPK, encoded by the gene) is well known, transcription is not activated by environmental stress and little is understood about how environmental stress signals lead to polyP accumulation. Previous work has shown that the transcriptional regulators DksA, RpoN (σ) and RpoE (σ) positively regulate polyP production, but not transcription, in . In this work, we examine the role of the alternative sigma factor RpoN and nitrogen starvation stress response pathways in controlling polyP synthesis. We show that the RpoN enhancer binding proteins GlnG and GlrR impact polyP production, and uncover a new role for the nitrogen phosphotransferase regulator PtsN (EIIA) as a positive regulator of polyP production, acting upstream of DksA, downstream of RpoN and apparently independently of RpoE. However, neither these regulatory proteins nor common nitrogen metabolites appear to act directly on PPK, and the precise mechanism(s) by which polyP production is modulated after stress remain(s) unclear. Unexpectedly, we also found that the genes that impact polyP production vary depending on the composition of the rich media in which the cells were grown before exposure to polyP-inducing stress. These results constitute progress towards deciphering the regulatory networks driving polyP production under stress, and highlight the remarkable complexity of this regulation and its connections to a broad range of stress-sensing pathways.
无机多聚磷酸盐（polyP）是细菌在应激环境条件下合成的，通过多种机制发挥作用，促进细胞存活。虽然合成多聚磷酸盐的激酶（PPK，由 基因编码）是众所周知的，但 转录不受环境应激激活，并且对于环境应激信号如何导致多聚磷酸盐积累知之甚少。先前的工作表明，转录调节因子 DksA、RpoN（σ）和 RpoE（σ）正向调节 中的多聚磷酸盐产生，但不调节 转录。在这项工作中，我们研究了替代 σ 因子 RpoN 和氮饥饿应激反应途径在控制多聚磷酸盐合成中的作用。我们表明，RpoN 增强子结合蛋白 GlnG 和 GlrR 影响多聚磷酸盐的产生，并揭示了氮磷酸转移酶调节蛋白 PtsN（EIIA）作为多聚磷酸盐产生的正调节剂的新作用，该作用位于 DksA 上游、RpoN 下游，显然独立于 RpoE。然而，这些调节蛋白和常见的氮代谢物似乎都不会直接作用于 PPK，应激后多聚磷酸盐产生的精确调节机制仍不清楚。出乎意料的是，我们还发现，影响多聚磷酸盐产生的基因取决于细胞在暴露于诱导多聚磷酸盐产生的应激之前在丰富培养基中的生长成分。这些结果构成了在应激条件下解析驱动多聚磷酸盐产生的调控网络的进展，并强调了这种调控的显著复杂性及其与广泛的应激感应途径的联系。
