Radeck Jara, Fritz Georg, Mascher Thorsten
Institute of Microbiology, Technische Universität (TU) Dresden, Dresden, Germany.
LOEWE-Center for Synthetic Microbiology (SYNMIKRO), Philipps-Universität Marburg, Marburg, Germany.
Curr Genet. 2017 Feb;63(1):79-90. doi: 10.1007/s00294-016-0624-0. Epub 2016 Jun 25.
The cell envelope stress response (CESR) encompasses all regulatory events that enable a cell to protect the integrity of its envelope, an essential structure of any bacterial cell. The underlying signaling network is particularly well understood in the Gram-positive model organism Bacillus subtilis. It consists of a number of two-component systems (2CS) and extracytoplasmic function σ factors that together regulate the production of both specific resistance determinants and general mechanisms to protect the envelope against antimicrobial peptides targeting the biogenesis of the cell wall. Here, we summarize the current picture of the B. subtilis CESR network, from the initial identification of the corresponding signaling devices to unraveling their interdependence and the underlying regulatory hierarchy within the network. In the course of detailed mechanistic studies, a number of novel signaling features could be described for the 2CSs involved in mediating CESR. This includes a novel class of so-called intramembrane-sensing histidine kinases (IM-HKs), which-instead of acting as stress sensors themselves-are activated via interprotein signal transfer. Some of these IM-HKs are involved in sensing the flux of antibiotic resistance transporters, a unique mechanism of responding to extracellular antibiotic challenge.
细胞包膜应激反应（CESR）涵盖了所有使细胞能够保护其包膜完整性的调节事件，而包膜是任何细菌细胞的基本结构。在革兰氏阳性模式生物枯草芽孢杆菌中，其潜在的信号网络已得到了很好的理解。它由许多双组分系统（2CS）和胞外功能σ因子组成，这些因子共同调节特定抗性决定因素的产生以及保护包膜免受针对细胞壁生物合成的抗菌肽影响的一般机制。在此，我们总结了枯草芽孢杆菌CESR网络的当前情况，从相应信号装置的最初鉴定到揭示它们之间的相互依赖性以及网络内潜在的调控层次结构。在详细的机制研究过程中，对于参与介导CESR的2CS可以描述一些新的信号特征。这包括一类新的所谓膜内感应组氨酸激酶（IM-HK），它们本身并非作为应激传感器，而是通过蛋白间信号传递被激活。其中一些IM-HK参与感知抗生素抗性转运蛋白的通量，这是一种应对细胞外抗生素挑战的独特机制。
