Understanding the Molecular Mechanism of Signal Transduction in LiaSR Two Component System in Bacillus Subtilis

Abstract

The Bacillus subtilis two-component system (TCS) LiaSR responds to environmental stresses inducing cell envelope damage. Here, the signal transduction mechanisms of LiaS/R are investigated in order to comprehend its uniqueness compared to other TCSs. My results indicate that the soluble portion of LiaS autophosphorylates and plays a bifunctional role towards LiaR. LiaR undergoes phosphorylation by acetyl phosphate in a time dependent manner. LiaR and its mutants bind to distinct regions on the liaSR promoter pre and post-phosphorylation. LiaR function is controlled independently by the N and C terminal domains. Characterization of the effector domain mutants created based on the homologous protein from Enterococcus faecalis suggested that the dimerization interface of LiaR lies on the N-terminal domain. Additionally, signal transduction between LiaSR and Staphylococcus aureus VraSR indicated possible in vivo interspecies cross-communication. In conclusion, my research provides comprehensive analysis of the LiaS/R signal transduction pathways regulating cellular responses in B. subtilis.