The cell envelope stress response of Bacillus subtilis: from static signaling devices to dynamic regulatory network
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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.
KeywordsCell wall antibiotic ECF sigma factor Lipid II cycle Stress response Signal transduction Two-component system
The authors would like to acknowledge the contributions of numerous co-workers of the Mascher group, who by their dedication, hard work and intellectual input shaped our picture of the cell envelope stress response of B. subtilis in the past decade.
Compliance with ethical standards
Work on the cell envelope stress response of B. subtilis in the Mascher and Fritz groups was continuously supported by Grants from the Deutsche Forschungsgemeinschaft (DFG) (Grants MA 3269, MA2837/1-3, and MA2837/3-1 to TM as well as Grant FR 3673/1-2 to GF).
Conflict of interest
The authors declare that they have no conflict of interest.
- Bernard R, Guiseppi A, Chippaux M, Foglino M, Denizot F (2007) Resistance to bacitracin in Bacillus subtilis: unexpected requirement of the BceAB ABC transporter in the control of expression of its own structural genes. J Bacteriol 189:8636–8642. doi: 10.1128/jb.01132-07 CrossRefPubMedPubMedCentralGoogle Scholar
- Cao M, Kobel PA, Morshedi MM, Wu MF, Paddon C, Helmann JD (2002) Defining the Bacillus subtilis σW regulon: a comparative analysis of promoter consensus search, run-off transcription/macroarray analysis (ROMA), and transcriptional profiling approaches. J Mol Biol 316:443–457. doi: 10.1006/jmbi.2001.5372 CrossRefPubMedGoogle Scholar
- Dintner S, Staron A, Berchtold E, Petri T, Mascher T, Gebhard S (2011) Co-evolution of ABC-transporters and two-component regulatory systems as resistance modules against antimicrobial peptides in Firmicutes bacteria. J Bacteriol 193:3851–3862. doi: 10.1128/JB.05175-11 CrossRefPubMedPubMedCentralGoogle Scholar
- Dintner S, Heermann R, Fang C, Jung K, Gebhard S (2014) A sensory complex consisting of an ATP-binding cassette transporter and a two-component regulatory system controls bacitracin resistance in Bacillus subtilis. J Biol Chem 289:27899–27910. doi: 10.1074/jbc.M114.596221 CrossRefPubMedPubMedCentralGoogle Scholar
- Hiron A, Falord M, Valle J, Debarbouille M, Msadek T (2011) Bacitracin and nisin resistance in Staphylococcus aureus: a novel pathway involving the BraS/BraR two-component system (SA2417/SA2418) and both the BraD/BraE and VraD/VraE ABC transporters. Mol Microbiol 81:602–622. doi: 10.1111/j.1365-2958.2011.07735.x CrossRefPubMedGoogle Scholar
- Jeong DW, Cho H, Jones MB, Shatzkes K, Sun F, Ji Q, Liu Q, Peterson SN, He C, Bae T (2012) The auxiliary protein complex SaePQ activates the phosphatase activity of sensor kinase SaeS in the SaeRS two-component system of Staphylococcus aureus. Mol Microbiol 86:331–348. doi: 10.1111/j.1365-2958.2012.08198.x CrossRefPubMedPubMedCentralGoogle Scholar
- Jordan S, Junker A, Helmann JD, Mascher T (2006) Regulation of LiaRS-dependent gene expression in Bacillus subtilis: identification of inhibitor proteins, regulator binding sites and target genes of a conserved cell envelope stress-sensing two-component system. J Bacteriol 188:5153–5166. doi: 10.1128/JB.00310-06 CrossRefPubMedPubMedCentralGoogle Scholar
- Kingston AW, Zhao H, Cook GM, Helmann JD (2014) Accumulation of heptaprenyl diphosphate sensitizes Bacillus subtilis to bacitracin: implications for the mechanism of resistance mediated by the BceAB transporter. Mol Microbiol 93:37–49. doi: 10.1111/mmi.12637 CrossRefPubMedPubMedCentralGoogle Scholar
- Pietiäinen M, Gardemeister M, Mecklin M, Leskela S, Sarvas M, Kontinen VP (2005) Cationic antimicrobial peptides elicit a complex stress response in Bacillus subtilis that involves ECF-type sigma factors and two-component signal transduction systems. Microbiology 151:1577–1592. doi: 10.1099/mic.0.27761-0 CrossRefPubMedGoogle Scholar
- Schrecke K, Staroń A, Mascher T (2012) Two-component signaling in the Gram-positive envelope stress response: intramembrane-sensing histidine kinases and accessory membrane proteins. In: Gross R, Beier D (eds) Two component systems in bacteria. Horizon Scientific Press, Hethersett, pp 199–229Google Scholar
- Wecke T, Zühlke D, Mäder U, Jordan S, Voigt B, Pelzer S, Labischinski H, Homuth G, Hecker M, Mascher T (2009) Daptomycin versus friulimicin B: in-depth profiling of Bacillus subtilis cell envelope stress responses. J Antimicrob Chemother 53:1619–1623. doi: 10.1128/aac.01046-08 CrossRefGoogle Scholar