SpoOA Starvation – activation of Spo0A
Spo0A during starvation
At the transition from logarithmic growth to stationary growth phase the Spo0A protein is phosphorylated through phosphoryl transfer by histidine autokinases KinA, KinB and KinC and phosphorelay proteins Spo0F and Spo0B. This results in a conformational change of Spo0A that initiates dimerization and subsequent activation of this transcriptional regulator 38. A simultaneous increase of σH levels instigates a positive feedback loop 39 that involves binding of Spo0A~P to the spo0H promoter as well as to its own, resulting in elevated levels of activated Spo0A~P. A promoter switch involving several different 0A boxes in the spo0A upstream region leads to induction of spo0A expression from the PS (sporulation) promoter through binding by σH-containing RNA polymerase and Spo0A~P 26. At the same time, the more upstream PV (vegetative) promoter is shut down through the involvement of one specific 0A box directly downstream PV 25. Additionally, at the posttranscriptional level, increased mRNA translation efficiency advances the rate of Spo0A synthesis 26. Taken together, these events result in elevated levels of activated Spo0A. Interestingly, noise in the phosphorelay results in pulsated accumulation of Spo0A~P, which may vary significantly between individual cells and furthermore enables postponement of the actual commitment to the dormant cell fate 41, 52, 56. This causes phenotypic variation of Spo0A-mediated responses 41, 55. Such responses rely on the binding of Spo0A~P to 0A boxes present in the upstream regions of 121 genes 42. Differences in promoter sensitivity to this regulator lead to a tight control system for gene activation or repression that will determine the eventual fate of the cell, with genes required for sporulation being activated last due to a high Spo0A~P level requirement 44. Nevertheless, the accumulation of Spo0A~P levels during starvation does not ensure spore formation and completion of sporulation per se, as irreversible commitment to sporulation does not occur until at least mother cell specific sigma factor σE is activated 57.