Novel σ B regulation modules of Gram-positive bacteria involve the use of complex hybrid histidine kinases

Abstract

A common bacterial strategy to cope with stressful conditions is the activation of alternative sigma factors that control specific regulons enabling targeted responses. In the human pathogen Bacillus cereus, activation of the major stress-responsive sigma factor s B is controlled by a signalling route that involves the multi-sensor hybrid histidine kinase RsbK. RsbK-type kinases are not restricted to the B. cereus group, but occur in a wide variety of other bacterial species, including members of the the low-GC Gram-positive genera Geobacillus and Paenibacillus as well as the high-GC actinobacteria. Genome context and protein sequence analyses of 118 RsbK homologues revealed extreme variability in N-terminal sensory as well as C-terminal regulatory domains and suggested that RsbK-type kinases are subject to complex fine-tuning systems, including sensitization and desensitization via methylation and demethylation within the helical domain preceding the H-box. The RsbK-mediated stress-responsive sigma factor activation mechanism that has evolved in B. cereus and the other species differs markedly from the extensively studied and highly conserved RsbRST-mediated s B activation route found in Bacillus subtilis and other low-GC Gram-positive bacteria. Implications for future research on sigma factor control mechanisms are presented and current knowledge gaps are briefly discussed.

Bacillus cereus cell response upon exposure to acid environment: toward the identification of potential biomarkers

“…In B. subtilis , σ B activity is controlled by RsbVW partner-switching, a mechanism which is highly conserved in species that contain σ B , including B. cereus strains (de Been et al, 2010, 2011). In non-stressed cells, σ B is present in an inactive form by complexation with the anti-sigma factor RsbW.…”

“…In the human pathogen B. cereus , the mechanism of σ B activation has only been studied more recently (van Schaik et al, 2004a,b, 2005, 2007; de Been et al, 2010, 2011). It has been shown that σ B activation is governed by a single PP2C-type phosphatase, RsbY, which carries an N-terminal response receiver (REC) domain (van Schaik et al, 2005).…”

“…RsbK contains both sensor histidine kinase and response regulator domains, and rsbK gene is located close to sigB on the genome of B. cereus ATCC 14579 ( Figure 2 ). They also realized a genome survey (de Been et al, 2011) indicating that RsbK and RsbY should constitute one functional module for the control of σ B activity in members of the B. cereus group, including the pathogens B. thuringiensis , B. anthracis and the psychrotolerant B. weihenstephanensis. One exception concerns the B. cytotoxicus genome which lacks the entire SigB operon, including sigB gene and the primary regulatory loci that control the SigB activity, rsbV and rsbW (Lapidus et al, 2008; Scott and Dyer, 2012).…”

“…B. cereus exhibits many differences with the Gram-positive model B. subtilis , such as the regulon of the general stress response (Anderson et al, 2005; de Been et al, 2011): this review will detail the vegetative cells acid stress response of B. cereus while data on the response of other Gram-positive bacteria upon exposure to low pH have been reviewed by Cotter and Hill (2003).…”

The General Stress Response σS Is Regulated by a Partner Switch in the Gram-negative Bacterium Shewanella oneidensis

“…Partner-switching systems are one among other mechanisms by which bacteria connect cue transmission and gene expression (27)(28)(29). The partner-switching system that regulates B consists of an antisigma factor with a kinase activity (RsbW), two phosphatases (RsbU and RsbP), and an anti-sigma antagonist (RsbV) that contains a phosphorylatable serine residue in its sequence.…”