Regulation of endospore formation in Bacillus subtilis

Key Points Endospores are formed by Bacillus, Clostridium and close relatives, generally in response to nutritional stress. The process of endospore formation is important both ecologically and practically, and it represents a simple, experimentally tractable example of cellular development and differentiation. Several hundred genes are specifically devoted to sporulation and the general regulatory pathways — involving five sigma factors and numerous other transcriptional regulators — are now well understood. Sporulation begins with a modified asymmetric cell division. The cell-division machinery is moved from its usual mid-cell position, to sites near each of the cell poles. One subpolar site is chosen for division. This generates the small prespore and the larger mother-cell compartments. Chromosome segregation into the prespore occurs, unusually, after septation, requiring a DNA transport protein, SpoIIIE. Compartment-specific transcription is initiated by cell-specific activation of two different sigma factors: σ F in the prespore and σ E in the mother cell. Complex regulatory mechanisms regulate the activity of these sigma factors so that they are activated at the right time and in the right compartment. σ F becomes active first, by regulatory mechanisms that are responsive to formation of the sporulation septum. Soon after septation, the cell-wall material in the septum is hydrolysed and the membranes of the septum migrate around the prespore, resulting in complete enclosure of the prespore by the mother-cell cytoplasm. This engulfment process generates the unique topological state by which endospores differ from all other spores. Late-gene expression in the two compartments is driven by σ G (prespore) and σ K (mother cell). These factors turn on new sets of genes that encode the proteins that are needed for formation of the protective cortex and spore-coat structures, and they bring about the massive physiological and biochemical changes that occur in the spore and that produce its unique resistance and dormancy properties. Spore formation in bacteria poses a number of biological problems of fundamental significance. Asymmetric cell division at the onset of sporulation is a powerful model for studying basic cell-cycle problems, including chromosome segregation and septum formation. Sporulation is one of the best understood examples of cellular development and differentiation. Fascinating problems posed by sporulation include the temporal and spatial