Abstract
Spx is a global transcriptional regulator present in low-GC Gram-positive bacteria, including the model bacterium Bacillus subtilis and various human pathogens. In B. subtilis, activation of Spx occurs in response to disulfide stress. We recently reported, however, that induction of Spx also occurs in response to cell wall stress, and that the molecular events that result in its activation under both stress conditions are mechanistically different. Here, we demonstrate that, in addition to up-regulation of spx transcription through the alternative sigma factor σM, full and timely activation of Spx-regulated genes by cell wall stress requires Spx stabilization by the anti-adaptor protein YirB. YirB is itself transcriptionally induced under cell wall stress, but not disulfide stress, and this induction requires the CssRS two-component system, which responds to both secretion stress and cell wall antibiotics. The yirB gene is repressed by YuxN, a divergently transcribed TetR family repressor, and CssR~P acts as an anti-repressor. Collectively, our results identify a physiological role for the YirB anti-adaptor protein and show that induction of the Spx regulon under disulfide and cell wall stress occurs through largely independent pathways.
Highlights
In its natural habitat, the soil-dwelling bacterium Bacillus subtilis is continuously exposed to stressful conditions that can compromise its survival
Disulfide stress induces the Spx regulon through post-translational events that involve both stabilization of Spx against proteolysis and protein oxidation
We previously reported that genes in the Spx regulon are induced in response to antibiotics that target the synthesis of the bacterial cell wall
Summary
The soil-dwelling bacterium Bacillus subtilis is continuously exposed to stressful conditions that can compromise its survival. Adaptation to stress often requires the interplay of multiple signaling pathways and regulators. Gene expression is controlled by modulation of the activity of transcription factors, which through precise molecular interactions redirect the activity of RNA polymerase at specific sets of genes [1]. In B. subtilis, for example, the cell envelope stress response is mediated by the individual or coordinated action of extracytoplasmic (ECF) sigma factors (e.g. σΜ, σW, and σX) [2], two-component signal transduction systems (e.g. LiaRS and BceSR) [3], and other transcription regulators (e.g. Spx) [2,3,4]. The activity of transcription factors can be regulated by changes in their expression or allosteric regulation of their activity. Adaptation to stress may involve regulated proteolysis of transcription factors [5]
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