Science, published online 6 October 2011, doi:10.1126/science.1208144

In prokaryotes, alternative sigma factors such as the Bacillus subtilis σB regulate RNA polymerase to activate target genes in response to diverse stresses. In a quantitative time-lapse microscopy study in individual cells, Locke et al. now show that energy stress induces a sustained series of stochastic pulses of σB activation, with the level of energy stress predominantly regulating the frequency of these pulses. The σB pulses arise through amplification of a noise-dependent process. By varying the levels of regulatory components coexpressed in the same operon as σB—the Rsbs (regulator of sigma B), including the kinase RsbW and the phosphatase RsbQP—the authors showed how pulses originate from a sensitive phosphoswitch that activates σB in response to fluctuations in the phosphatase/kinase ratio. Autoregulation results in a mixed positive-negative feedback loop, allowing for both amplification and termination of pulses. RsbQP expression is at the center of this mechanism: high levels engage the positive feedback loop to activate more σB, leading to higher induction of RsbW that ultimately turns the system off, leading to a pulse. The results show that bacteria implement highly dynamic, noise-dependent pulsatile response programs to dynamically balance the benefits and costs of σB activation.