Stimulus perception and two-component signal transduction within the regulatory network of cell envelope stress response in Bacillus subtilis

对环境条件进行长期、灵敏的监测是细菌在土壤生态系统等复杂生境中生存的先决条件。双组分信号转导是一种普遍存在的感知环境参数的机制（输入），并由于环境参数的变化而诱导适当的细胞反应（输出）。我们最近在枯草芽孢杆菌细胞壁应激反应中发现了一种新的信号转导机制，该机制是由膜内感知组氨酸激酶介导的。这些蛋白缺乏胞质外传感结构域，可能直接在膜界面监测细胞包膜完整性。该蛋白家族的第一个例子，枯草芽孢杆菌的LiaS，感知脂质II周期的扰动，这是细胞壁稳态的关键步骤。在这里，我们提出了相应的谎言双组分系统的研究，这是一个关键的调节迟稳定相位信号级联。我们将重点研究其信号转导的三个方面：首先，我们想研究组氨酸激酶LiaS的膜内感知机制。第二部分将讨论已鉴定的liartarget基因的生物学功能。该调控的三个成员编码假定的转录调控因子（一个替代因子和两个响应调控因子作为双组分系统的一部分）。因此，本提案第三部分的主题将是在体内和体外鉴定它们的靶基因。

A permanent and sensitive monitoring of environmental conditions is a prerequisite for the survival of bacteria living in a complex habitat such as the soil ecosystem. Two-component signal transduction is a ubiquitously distributed mechanism to sense parameters of the environment (input) and induce appropriate cellular responses as a result of changes thereof (output). We have recently identified a novel signal transducing mechanism in the cell wall stress response of Bacillus subtilis, mediated by intram embrane sensing histidine kinases. These proteins lack an extracytoplasmic sensing domain, and presumably monitor cell envelope integrity directly at the membrane interface. The first example of this protein family, LiaS of B. subtilis, senses perturbations of the lipid II cycle, a crucial step for cell wall homeostasis. Here, we propose the investigation of the corresponding LiaRS two-component system, the key regulator of a late stationary phase signalling cascade. We will focus on three aspects of its signal transduction: First, we want to investigate the intramembrane sensing mechanism of the histidine kinase LiaS. The second part will address the biological function of the identified LiaRStarget genes. Three members of this regulon encode putative transcriptional regulators (one alternative s factor and two response regulators as part of two-component systems). Therefore, the subject of the third part of this proposal will be the identification of their target genes, in vivo and in vitro.