Bacterial cell cycle and growth phase switch by the essential transcriptional regulator CtrA

Many bacteria acquire dissemination and virulence traits in G1-phase. CtrA, an essential and conserved cell cycle transcriptional regulator identified in the dimorphic alpha-proteobacterium Caulobacter crescentus, first activates promoters in late S-phase and then mysteriously switches to different target promoters in G1-phase. We uncovered a highly conserved determinant in the DNA-binding domain (DBD) of CtrA uncoupling this promoter switch. We also show that it reprograms CtrA occupancy in stationary cells inducing a (p)ppGpp alarmone signal perceived by the RNA polymerase beta subunit. A simple side chain modification in a critical residue within the core DBD imposes opposing developmental phenotypes and transcriptional activities of CtrA. A naturally occurring polymorphism in the rickettsial DBD resembles a mutation that drives CtrA towards activation of the dispersal (G1-phase) program in Caulobacter. Hence, we propose that this determinant dictates promoter reprogramming during the growth transition of obligate intracellular rickettsia differentiating from replicative cells into dispersal cells.