title: Immediate and heterogeneous response of the LiaFSR two-component system of Bacillus subtilis to the peptide antibiotic bacitracin.
abstract: BACKGROUND
  Two-component signal transduction systems are one means of bacteria to respond to external stimuli. The LiaFSR two-component system of Bacillus subtilis consists of a regular two-component system LiaRS comprising the core Histidine Kinase (HK) LiaS and the Response Regulator (RR) LiaR and additionally the accessory protein LiaF, which acts as a negative regulator of LiaRS-dependent signal transduction. The complete LiaFSR system was shown to respond to various peptide antibiotics interfering with cell wall biosynthesis, including bacitracin.
  
  
  RESULTS
  Here we study the response of the LiaFSR system to various concentrations of the peptide antibiotic bacitracin. Using quantitative fluorescence microscopy, we performed a whole population study analyzed on the single cell level. We investigated switching from the non-induced 'OFF' state into the bacitracin-induced 'ON' state by monitoring gene expression of a fluorescent reporter from the RR-regulated liaI promoter. We found that switching into the 'ON' state occurred within less than 20 min in a well-defined switching window, independent of the bacitracin concentration. The switching rate and the basal expression rate decreased at low bacitracin concentrations, establishing clear heterogeneity 60 min after bacitracin induction. Finally, we performed time-lapse microscopy of single cells confirming the quantitative response as obtained in the whole population analysis for high bacitracin concentrations.
  
  
  CONCLUSIONS
  The LiaFSR system exhibits an immediate, heterogeneous and graded response to the inducer bacitracin in the exponential growth phase.
authors: Center for NanoScience, Ludwig-Maximilians-University, Fakultät für Physik, Munich, Germany.
authors: Sara
authors: S
authors: Kesel
authors: Andreas
authors: A
authors: Mader
authors: Carolin
authors: C
authors: Höfler
authors: Thorsten
authors: T
authors: Mascher
authors: Madeleine
authors: M
authors: Leisner
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000166:cytology / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D001414:Bacitracin / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D008563:Membrane Lipids / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C490532:LiaRS protein, Bacillus subtilis; D008563:Membrane Lipids; D001414:Bacitracin