The alternative sigma factor σ^X mediates competence shut-off at the cell pole in Streptococcus pneumoniae

Competence is a widespread bacterial differentiation program driving antibiotic resistance and virulence in many pathogens. Here, we studied the spatiotemporal localization dynamics of the key regulators that master the two intertwined and transient transcription waves defining competence in Streptococcus pneumoniae. The first wave relies on the stress-inducible phosphorelay between ComD and ComE proteins, and the second on the alternative sigma factor σ^X, which directs the expression of the DprA protein that turns off competence through interaction with phosphorylated ComE. We found that ComD, σ^X and DprA stably co-localize at one pole in competent cells, with σ^X physically conveying DprA next to ComD. Through this polar DprA targeting function, σ^X mediates the timely shut-off of the pneumococcal competence cycle, preserving cell fitness. Altogether, this study unveils an unprecedented role for a transcription σ factor in spatially coordinating the negative feedback loop of its own genetic circuit.