Bacillus Subtilis

Pre-sporulation stage -
the vegetative state of B. subtilis cells

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 1.Vegetative state

Stress-inducing fluctuations in the environment, particularly limitations in nutrient availability, function as signals for bacterial adaptation. These signals are transferred into the cell via signal transduction systems and bring about cellular responses such as altered gene expression (described extensively in 1). One well-described signal transduction system for cellular developmental strategies of B. subtilis like biofilm formation and sporulation, is called the phosphorelay 2. Through the phosphorelay the key sporulation regulator Spo0A is phosphorylated and thus activated. During vegetative growth the expression of genes involved in these survival processes is inhibited via several different mechanisms. For instance, nutritional conditions causing high growth rates are reflected by increased levels of GTP, which are sensed and bound by CodY. This causes repression of spo0A transcription 3. This inhibition of sporulation is lifted when the cells enter stationary phase and GTP levels decrease - most likely due to accumulation of the stringent response 'alarmone' (p)ppGpp 4,5. Another signalling molecule called cyclic-di-AMP plays an important role in the timing of sporulation initiation 6.


Other key players in sporulation inhibition are the transition state regulators AbrB, SinR and ScoC 7. On the posttranslational level phosphorylation and dephosphorylation events of proteins control the levels of active (regulatory) proteins that, together with the transcriptional control, tightly regulate the cell's response to environmental signals 8.



Sporulation cycle of Bacillus subtilis




Schematic representation of sporulation-specific gene transcription regulation during vegetative growth

During vegetative growth, the transition state regulators AbrB, ScoC and SinR (indicated in green ovals) prevent sporulation by repressing a subset of genes (indicated in red lined boxes) and activating others (indicating in blue lined boxes). Active sigma factors are indicated as blue hexagons. Inactive proteins are indicated as grey ovals. Active and inactive genes important for the sporulation process are indicated as wide black arrows and wide grey arrows, respectively. A positive effect of proteins on gene transcription is represented by black arrowed lines. A negative effect by black stopped lines. Active and inactive promoters upstream of a gene are indicated as green arrows and red arrows, respectively.