Cell Envelope Stress Response in Bacillus licheniformis : Integrating Comparative Genomics, Transcriptional Profiling, and Regulon Mining To Decipher a Complex Regulatory Network

Abstract

ABSTRACT The envelope is an essential structure of the bacterial cell, and maintaining its integrity is a prerequisite for survival. To ensure proper function, transmembrane signal-transducing systems, such as two-component systems (TCS) and extracytoplasmic function (ECF) σ factors, closely monitor its condition and respond to harmful perturbations. Both systems consist of a transmembrane sensor protein (histidine kinase or anti-σ factor, respectively) and a corresponding cytoplasmic transcriptional regulator (response regulator or σ factor, respectively) that mediates the cellular response through differential gene expression. The regulatory network of the cell envelope stress response is well studied in the gram-positive model organism Bacillus subtilis . It consists of at least two ECF σ factors and four two-component systems. In this study, we describe the corresponding network in a close relative, Bacillus licheniformis . Based on sequence homology, domain architecture, and genomic context, we identified five TCS and eight ECF σ factors as potential candidate regulatory systems mediating cell envelope stress response in this organism. We characterized the corresponding regulatory network by comparative transcriptomics and regulon mining as an initial screening tool. Subsequent in-depth transcriptional profiling was applied to define the inducer specificity of each identified cell envelope stress sensor. A total of three TCS and seven ECF σ factors were shown to be induced by cell envelope stress in B. licheniformis. We noted a number of significant differences, indicative of a regulatory divergence between the two Bacillus species, in addition to the expected overlap in the respective responses.