Sporulation of Bacillus subtilis
Introduction
Actively growing cells of Bacillus subtilis are induced to differentiate into spores by starvation for carbon, nitrogen or, in some circumstances a phosphorus source. Spore formation takes about 7 h at 37°C. Initiation signals result in activation of the master transcription regulator, Spo0A, by phosphorylation. Activated Spo0A, among other things, triggers the asymmetric sporulation division and transcription of the spoIIA, spoIIE and spoIIG loci, which encode key developmental regulators. The sporulation division produces two distinct cells with very different fates, the smaller prespore (also known as forespore), which develops into the spore, and the mother cell, which is necessary for spore formation but ultimately lyses (programmed cell death). Soon after the division distinct programs of gene expression are initiated in the two cell types. These are directed by sporulation-specific RNA polymerase σ factors, σF in the prespore and σE in the mother cell. About 1 h after division, the prespore is engulfed by the mother cell. On completion of engulfment, there is another substantial change in transcription, with σG becoming active in the prespore and σK in the mother cell (Figure 1). These global changes in gene regulation are coupled to morphogenesis and to each other by intercompartmental signaling, eventually leading to the development of the resistances that characterize the mature spore.
Spore formation is a very active research subject, and we discuss only some topics. For more extensive coverage, and for citations to the earlier literature we refer to fuller reviews 1., 2., 3.. Assembly of spore surface layers, spore resistance and spore germination are not considered here. Three recent reviews discuss these topics in depth 4., 5., 6..
In this review, we discuss the regulation of gene expression during spore formation and the coordination of gene expression with morphological changes.
Section snippets
Initiation of sporulation
Genomic analysis has indicated that Spo0A directly regulates the transcription of 121 genes, with about one-third being activated and the remainder repressed. This group includes several transcription factors; a further ∼400 genes are indirectly controlled by Spo0A 7., 8.•. The molecular details of the interaction of Spo0A with its target DNA, the ‘Spo0A box’, have now been analyzed with a crystal structure [9]. Activation of Spo0A goes through several phases. Initial activation at the end of
Morphogenesis and chromosome partitioning
During sporulation, the bacterial cell is dramatically reorganized to generate two daughter cells of very different size and fate, the smaller prespore and larger mother cell. The nucleoids of the vegetative cell are remodeled into a continuous structure, the axial filament of chromatin, which extends the length of the cell (Figure 3). RacA has been identified as a protein produced during sporulation that binds the chromosome and the polar division protein DivIVA, acting as a bridge connecting
Compartmentalized gene expression
Immediately after the asymmetric division and before a chromosome has completely partitioned into the prespore, σF becomes active exclusively in the prespore (Figure 1). In the pre-divisional cell σF is held inactivate by the anti-σ factor SpoIIAB; this inhibition is reversed by the anti-anti-σ factor SpoIIAA. SpoIIAA is regulated by its phosphorylation state; it is inactive when phosphorylated by SpoIIAB (a kinase as well as an anti-σ) and active when it is dephosphorylated by SpoIIE (Figure 4
Conclusions
The key players in the pattern of gene expression are Spo0A, σH, σF, σE, σG and σK. A good understanding of their complex regulation is developing (Figure 2, Figure 4). Microarray analysis has identified RacA, which is critical for the previously neglected Stage I of spore formation, axial filament formation. The mechanism of polar FtsZ ring formation has become clearer, although the choice of location remains to be explained (Figure 3). We are beginning to understand how guanine nucleotides,
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
Research in the laboratory of PJP was supported by Public Health Service Grant GM43577 from the National Institutes of Health. DWH is a National Science Foundation Postdoctoral Fellow in Microbial Biology.
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