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

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) factors, closely monitor its condition and respond to harmful perturbations. Both systems consist of a transmembrane sensor protein (histidine kinase or antifactor, respectively) and a corresponding cytoplasmic transcriptional regulator (response regulator or 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 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 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 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.

CpsY Influences Streptococcus iniae Cell Wall Adaptations Important for Neutrophil Intracellular Survival

“…In L. lactis the CesSR TCS responds to lysozyme-induced cell envelope stress by activation of OatA through the intermediate SpxB regulator (80). CesSR homologs have also been shown to respond to cell envelope stress in S. pneumoniae (22,28), S. mutans (75), Staphylococcus aureus (45), Bacillus licheniformis (84) and Bacillus subtilis (36). S. iniae also contains a CesSR homolog; however, its functionality in the cell envelope stress response is unknown.…”

Resistance to Bacitracin in Bacillus subtilis : Unexpected Requirement of the BceAB ABC Transporter in the Control of Expression of Its Own Structural Genes

“…UPP phosphatases of the PAP2 family, such as BcrC in Bacillus subtilis (formerly YwoA) (3), are found in some gram-positive bacteria, in which they compete with bacitracin for UPP, thus conferring a certain level of protection on the cells (4,23). The bacitracin producer Bacillus licheniformis ATCC 10716 possess two PAP2 family members, BcrC and a BcrC-like protein (YP_080959) (21,27,38). However, in addition to the UPP phosphatases, some gram-positive bacteria also possess an ABC transporter(s), which is an even more efficient bacitracin protection system.…”

“…BcrAB from B. licheniformis and BcrAB from E. faecalis belong to family 7, and both the elements controlling the expression of their structural genes and the way these elements operate differ (21). Family 9 contains BceAB from B. subtilis , YtsCD from B. licheniformis, and MbrAB from S. mutans, each genetically and functionally linked to a signal transduction system including a histidine kinase and a response regulator (4,22,36,38).…”

Importance of systems biology in engineering microbes for biofuel production

“…However, integrated models have been used to identify essential genes [ 42], transcriptional elements [11 ₃₃ ], regulatory circuits [ 43], and stress response [ 10] in many microorganisms. Such existing models provide valuable information about cellular activi-ties and may be used to pinpoint responses that prevent optimal production.…”