Divergence of the SigB regulon and pathogenesis of the Bacillus cereus sensu lato group

Abstract

BackgroundThe Bacillus cereus sensu lato group currently includes seven species (B. cereus, B. anthracis, B. mycoides, B. pseudomycoides, B. thuringiensis, B. weihenstephanensis and B. cytotoxicus) that recent phylogenetic and phylogenomic analyses suggest are likely a single species, despite their varied phenotypes. Although horizontal gene transfer and insertion-deletion events are clearly important for promoting divergence among these genomes, recent studies have demonstrated that a major basis for phenotypic diversity in these organisms may be differential regulation of the highly similar gene content shared by these organisms. To explore this hypothesis, we used an in silico approach to evaluate the relationship of pathogenic potential and the divergence of the SigB-dependent general stress response within the B. cereus sensu lato group, since SigB has been demonstrated to support pathogenesis in Bacillus, Listeria and Staphylococcus species.ResultsDuring the divergence of these organisms from a common “SigB-less” ancestor, the placement of SigB promoters at varied locations in the B. cereus sensu lato genomes predict alternative structures for the SigB regulon in different organisms. Predicted promoter changes suggesting differential transcriptional control of a common gene pool predominate over evidence of indels or horizontal gene transfer for explaining SigB regulon divergence.ConclusionsFour lineages of the SigB regulon have arisen that encompass different gene contents and suggest different strategies for supporting pathogenesis. This is consistent with the hypothesis that divergence within the B. cereus sensu lato group rests in part on alternative strategies for regulation of a common gene pool.

Divergence of protein-coding capacity and regulation in the Bacillus cereus sensu lato group

“…Strikingly, the genomic relationships between these organisms, shown in Figure 2 , were identical to those that we had previously identified, based on the predicted structure of the generalized stress response regulon controlled by SigB [ 21 ]. Those observations are summarized in Table 2 for comparison.…”

“…By contrast, organisms in Clades A and B of the present study, many of which were associated with food poisoning outbreaks, carry a SigB regulon that either harbors only the core SigB regulon genes found in all B. cereus sensu lato organisms (Clade B), or have added to this core SigB regulon additional genes (Clade A) that may act enhance the stress response of these organisms during the response to deleterious environmental conditions (e.g., cold temperatures, UV light) that may be found in food processing facilities. Importantly, differences between the SigB regulon structure in these four clades are primarily a consequence of whether components of the core genome are/are not driven by a SigB promoter [ 21 ], rather than differences in gene content between these clades; the majority of genes contained in the SigB regulons of these organisms are included in the core genomes of these organisms, and their differences lie in whether their transcription is controlled by SigB. That we arrived at the same genomic relationships between these organisms using two entirely different approaches suggests an underlying organization in this population that has not been previously noted.…”

“…In our experience, CD-hit offered comparable results to other orthology search programs such as OrthoMCL [ 20 ] and was computationally much faster. Similar to previously described methods performed by our group [ 21 ], this cutoff required an 85% sequence identity across 85% sequence length for CD-hit while all other parameters remained at the default values. Manually inspecting this output, we confirmed that a representative protein from each organism was grouped with other similar proteins to form the orthologous clusters.…”

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

“…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). Orthologous RsbKY signaling modules were found in four other Bacilli outside the B. cereus group.…”

Complete genome sequence of the nematicidal Bacillus thuringiensis MYBT18247

“…Bacillus thuringiensis is a member of the genus Bacillus, which are low GC-content, Gram-positive bacteria with a respiratory metabolism and the ability to form heat-and desiccation-resistant endospores [11,17,18]. Within this genus, B. thuringiensis is a member of the Bacillus cereus sensu lato species group which originally contained seven different species (B. cereus, B. anthracis, B. thuringiensis, B. mycoides, B. pseudomycoides, B. weihenstephanensis, B. cytotoxicus [17][18][19][20][21][22][23][24][25]). Historically, most pathogenic and phenotypic properties were used for strain classification.…”