Glucose Induces ECF Sigma Factor Genes, sigX and sigM, Independent of Cognate Anti-sigma Factors through Acetylation of CshA in Bacillus subtilis

Abstract

Extracytoplasmic function (ECF) σ factors have roles related to cell envelope and/or cell membrane functions, in addition to other cellular functions. Without cell-surface stresses, ECF σ factors are sequestered by the cognate anti-σ factor, leading to inactivation and the resultant repression of regulons due to the inhibition of transcription of their own genes. Bacillus subtilis has seven ECF σ factors including σX and σM that transcribe their own structural genes. Here, we report that glucose addition to the medium induced sigX and sigM transcription independent of their anti-σ factors. This induction was dependent on an intracellular acetyl-CoA pool. Transposon mutagenesis searching for the mutants showing no induction of sigX and sigM revealed that the cshA gene encoding DEAD-box RNA helicase is required for gene induction. Global analysis of the acetylome in B. subtilis showed CshA has two acetylated lysine residues. We found that in a cshA mutant with acetylation-abolishing K to R exchange mutations, glucose induction of sigX and sigM was abolished and that glucose addition stimulated acetylation of CshA in the wild type strain. Thus, we present a model wherein glucose addition results in a larger acetyl-CoA pool, probably leading to increased levels of acetylated CshA. CshA is known to associate with RNA polymerase (RNAP), and thus RNAP with acetylated CshA could stimulate the autoregulation of sigX and sigM. This is a unique model showing a functional link between nutritional signals and the basal transcription machinery.

Deciphering the essentiality and function of the anti‐σM factors in Bacillus subtilis

“…Overall, our data indicate that YhdK is needed for perception of cell wall stress signals, and for the efficient function of the YhdL anti‐sigma factor in sequestration of SigM. However, the YhdLK complex may not be the only pathway that can serve to activate SigM‐dependent gene expression and an alternative pathway involving acetylation of the RNAP associated CshA helicase has also been suggested (Ogura and Asai, ).…”

Regulation, Function, and Detection of Protein Acetylation in Bacteria

“…The CTD of RpoA makes direct contacts with DNA elements and transcription factors (107,108), providing a potential mechanism by which acetylation can rapidly alter transcription in response to environmental cues (97,104,105,(107)(108)(109). In B. subtilis, an RNA helicase (CshA) that associates with RNAP is required for glucose induction of SigX-and SigM-dependent genes (110). This induction relies on the acetyl-CoA pool and the acetylation of two CshA residues.…”

Anti-sigma factor-mediated cell surface stress responses in <i>Bacillus</i> <i>subtilis</i>

“…These observations indicate that the activity of ECF sigma factors is sometimes regulated by an antisigma factor via the universal effects of membrane degeneration; it is thus plausible that multiple stress response systems should be launched rapidly and simultaneously in order to confront an immediate and diverse environmental and internal exchange. Notably, glucose addition leads to increased levels of acetylated CshA, which is known to associate with RNA polymerase, and RNA polymerase bound to acetylated CshA could preferentially bind σ X and σ M (Ogura and Asai, 2016). This is a unique model of a regulatory link between ECF sigma factors and intracellular nutritional signals as well as extracellular stress signals, independent of anti-sigma factors.…”