Developmental switch within the bacterial cell cycle 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, mysteriously switches from activating promoters in late S-phase to a different set in G1-phase. We found that a core and highly conserved determinant in the DNA-binding domain (DBD) of CtrA governs this promoter switch and that it is also required for promoter reprogramming in stationary phase in response to a (p)ppGpp alarmone signal perceived by the RNA polymerase beta subunit. A simple side chain modification in one critical residue of this DBD confers opposing developmental phenotypes and transcriptional activities. This region is also central to understanding the developmental reprogramming in the obligate intracellular Rickettsiae where replicative cells develop into dispersal cells and a naturally occurring polymorphism in the rickettsial DBD resembles a mutation that drives CtrA towards activation of the dispersal (G1-phase) program in Caulobacter. Examination of CtrA whole genome binding/occupancy (ChIP-Seq) in WT Caulobacter crescentus and mutants