Regulation of LiaRS-Dependent Gene Expression inBacillus subtilis: Identification of Inhibitor Proteins, Regulator Binding Sites, and Target Genes of a Conserved Cell Envelope Stress-Sensing Two-Component System

Publisher Website
Google Scholar
Abstract
The regulatory network of the cell envelope stress response inBacillus subtilisinvolves both extracytoplasmic function σ-factors and two-component signal transducing systems. One such system, LiaRS, responds to cell wall antibiotics that interfere with the undecaprenol cycle and to perturbation of the cytoplasmic membrane. It is encoded by the last two genes of theliaIHGFSRlocus. Here, we analyzed the expression of two LiaR-dependent operons,liaIHGFSRandyhcYZ-yhdA, and characterized a palindromic sequence required for LiaR-dependent activation. Since induction of the strongliaIpromoter leads to bothliaIHandliaIHGFRStranscripts, LiaR is positively autoregulated. Systematic deletion analysis of theliaIoperon revealed that LiaF is a potent negative regulator of LiaR-dependent gene expression: a nonpolarliaFdeletion led to constitutive activation of both characterized LiaR-dependent promoters. TheliaFgene is conserved in both sequence and genomic context in theFirmicutesgroup of gram-positive bacteria, located directly upstream ofliaSRorthologs. LiaH, a homolog ofEscherichia coliphage shock protein A, also plays a more subtle role in negatively modulating the bacitracin-inducible expression from LiaR-dependent promoters. Our results support a model in which the LiaFRS module integrates both positive and negative feedback loops to transduce cell envelope stress signals.