title: The cell envelope stress response of Bacillus subtilis: from static signaling devices to dynamic regulatory network.
abstract: 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.
authors.affiliation: Institute of Microbiology, Technische Universität (TU) Dresden, Dresden, Germany.
authors.forename: Jara
authors.initials: J
authors.lastname: Radeck
authors.affiliation: LOEWE-Center for Synthetic Microbiology (SYNMIKRO), Philipps-Universität Marburg, Marburg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Fritz
authors.affiliation: Institute of Microbiology, Technische Universität (TU) Dresden, Dresden, Germany. Thorsten.Mascher@tu-dresden.de.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Mascher
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects / Q000502:physiology*; D001426:Bacterial Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism*; D024881:Drug Resistance, Bacterial; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D053263:Gene Regulatory Networks; D006706:Homeostasis; D050356:Lipid Metabolism; D011485:Protein Binding; D053038:Quorum Sensing / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D014157:Transcription Factors; D000249:Adenosine Monophosphate
keywords: Cell wall antibiotic; ECF sigma factor; Lipid II cycle; Signal transduction; Stress response; Two-component system