Two-stage regulation of an anti-sigma factor determines developmental fate during bacterial endospore formation.

During endospore formation in Bacillus subtilis an asymmetric division produces two cells, forespore and mother cell, which follow different developmental paths. Commitment to the forespore-specific developmental path is controlled in part by the activation of the forespore-specific RNA polymerase sigma factor, sigma F. Activity of sigma F is inhibited in the mother cell by the anti-sigma factor SpoIIAB. In the forespore, sigma F directs transcription of the structural gene for sigma G. However, sigma G does not become active until after engulfment of the forespore is complete. This sigma G activity is dependent upon the products of the spoIIIA operon. We showed that sigma G is present but mostly inactive in a spoIIIA mutant. We also demonstrated that the anti-sigma factor SpoIIAB can bind to sigma G in vitro. Moreover, a mutant form of sigma G that binds SpoIIAB inefficiently in vitro was shown to function independently of SpoIIIA during sporulation. These and previously reported results support a model in which SpoIIAB functions as an inhibitor of sigma G activity during sporulation. Therefore, we propose that the anti-sigma factor SpoIIAB antagonizes both sigma F and sigma G activities, and that this antagonism is relieved in the forespore in two stages. In the first stage, which follows septation, a SpoIIAA-dependent mechanism partially relieves SpoIIAB inhibition of sigma F activity in the forespore. In the second stage, which follows forespore engulfment, a SpoIIIA-dependent process inactivates SpoIIAB in the forespore, resulting in the activation of sigma G.