Chen Xingru, Alakavuklar Melene A, Fiebig Aretha, Crosson Sean
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan USA.
bioRxiv. 2023 Oct 11:2023.04.15.536747. doi: 10.1101/2023.04.15.536747.
A multi-layered structure known as the cell envelope separates the controlled interior of bacterial cells from a fluctuating physical and chemical environment. The transcription of genes that determine cell envelope structure and function is commonly regulated by two-component signaling systems (TCS), comprising a sensor histidine kinase and a cognate response regulator. To identify TCS genes that contribute to cell envelope function in the intracellular mammalian pathogen, , we subjected a collection of non-essential TCS deletion mutants to compounds that disrupt cell membranes and the peptidoglycan cell wall. Our screen led to the discovery of three TCS proteins that coordinately function to confer resistance to cell envelope stressors and to support replication in the intracellular niche. This tripartite regulatory system includes the known cell envelope regulator, CenR, and a previously uncharacterized TCS, EssR-EssS, which is widely conserved in . The CenR and EssR response regulators bind a shared set of sites on the chromosomes to control transcription of an overlapping set of genes with cell envelope functions. CenR directly interacts with EssR and functions to stimulate phosphoryl transfer from the EssS kinase to EssR, while CenR and EssR control the cellular levels of each other via a post-transcriptional mechanism. Our data provide evidence for a new mode of TCS cross-regulation in which a non-cognate response regulator affects both the activity and protein levels of a cognate TCS protein pair.
一种被称为细胞包膜的多层结构将细菌细胞受控制的内部与波动的物理和化学环境分隔开来。决定细胞包膜结构和功能的基因转录通常由双组分信号系统（TCS）调控，该系统由一个传感组氨酸激酶和一个同源反应调节因子组成。为了鉴定在细胞内哺乳动物病原体中对细胞包膜功能有贡献的TCS基因，我们让一组非必需的TCS缺失突变体接触破坏细胞膜和肽聚糖细胞壁的化合物。我们的筛选发现了三种TCS蛋白，它们协同发挥作用，赋予对细胞包膜应激源的抗性，并支持在细胞内生态位中的复制。这个三方调节系统包括已知的细胞包膜调节因子CenR和一个以前未被表征的TCS，EssR - EssS，它在……中广泛保守。CenR和EssR反应调节因子结合在……染色体上的一组共同位点，以控制一组具有细胞包膜功能的重叠基因的转录。CenR直接与EssR相互作用，并促进磷酸基团从EssS激酶转移到EssR，而CenR和EssR通过转录后机制相互控制彼此的细胞水平。我们的数据为TCS交叉调节的一种新模式提供了证据，即一个非同源反应调节因子影响同源TCS蛋白对的活性和蛋白质水平。
