Spo0A∼P Imposes a Temporal Gate for the Bimodal Expression of Competence in Bacillus subtilis

Abstract

ComK transcriptionally controls competence for the uptake of transforming DNA in Bacillus subtilis. Only 10%–20% of the cells in a clonal population are randomly selected for competence. Because ComK activates its own promoter, cells exceeding a threshold amount of ComK trigger a positive feedback loop, transitioning to the competence ON state. The transition rate increases to a maximum during the approach to stationary phase and then decreases, with most cells remaining OFF. The average basal rate of comK transcription increases transiently, defining a window of opportunity for transitions and accounting for the heterogeneity of competent populations. We show that as the concentration of the response regulator Spo0A∼P increases during the entry to stationary phase it first induces comK promoter activity and then represses it by direct binding. Spo0A∼P activates by antagonizing the repressor, Rok. This amplifies an inherent increase in basal level comK promoter activity that takes place during the approach to stationary phase and is a general feature of core promoters, serving to couple the probability of competence transitions to growth rate. Competence transitions are thus regulated by growth rate and temporally controlled by the complex mechanisms that govern the formation of Spo0A∼P. On the level of individual cells, the fate-determining noise for competence is intrinsic to the comK promoter. This overall mechanism has been stochastically simulated and shown to be plausible. Thus, a deterministic mechanism modulates an inherently stochastic process.

Growth Phase and pH Influence Peptide Signaling for Competence Development in Streptococcus mutans

“…Then, once the competence cascade is shut off, cells regain responsiveness to XIP in late-exponential phase, as evinced by the fact that neutralization of the medium or resuspension of cells at an OD of 0.8 in supernatants at an OD of 0.2 or in fresh FMC medium restored the inducibility of comX by XIP. Similar types of circuits that shut off competence in B. subtilis (45) and S. pneumoniae (46,47) have been characterized recently. Evidence for the existence of factors in S. mutans that can control comX expression and impact the ability of ComX to activate comYA and other late com genes has been presented in studies from our laboratory with the rcrRPQ operon (48).…”

Bacillus subtilis Mutants with Knockouts of the Genes Encoding Ribonucleases RNase Y and RNase J1 Are Viable, with Major Defects in Cell Morphology, Sporulation, and Competence

“…However, in a previous tiling array experiment (16), a number of key sporulation genes showed increased expression levels in RNase J1 and RNase Y depletion mutants, including those of the master regulator Spo0A (RNases J1 and Y) and its modulators Spo0B and Spo0E (RNase J1) (see Table S2 in the supplemental material). Phosphorylated SpoOA also plays a key role in competence by first indirectly increasing the expression level of ComK, the master competence regulator, and then directly inhibiting its transcription by binding to its promoter (26). Interestingly, levels of the comK mRNA were also significantly increased in RNase J1-depleted strains (16), while those of other important regulators were decreased in either RNase J1 (ComS and ComQ) or RNase Y (ComN) mutants.…”

What renders Bacilli genetically competent? A gaze beyond the model organism

“…At the end of the exponential growth phase, expression of abrB is repressed by increasing concentrations of the activated response regulator Spo0A~P (O'Reilly and Devine 1997). Spo0A~P further acts as an anti-repressor that antagonizes Rok by directly binding to P comK , initially displaying an inducing but, upon its accumulation, a repressing impact on promoter activity (Mirouze et al 2012).…”