Regulation of the transcription factor CdnL promotes adaptation to nutrient stress in Caulobacter
In response to nutrient deprivation, bacteria activate a conserved stress response pathway called the stringent response (SR). In Caulobacter crescentus, SpoT synthesizes the secondary messengers (p)ppGpp, which affect transcriptional reprogramming by binding to RNA polymerase to downregulate anabolic gene transcription. (p)ppGpp can also impact the expression of anabolic genes by controlling the levels and activities of their transcriptional regulators. In Caulobacter, a major regulator of anabolic genes is the conserved transcription factor CdnL. If and how CdnL is controlled during the SR and why that might be functionally important is unclear. Here, we show that CdnL is regulated post-translationally in a manner dependent on SpoT and the ClpXP protease. We find that stabilization of CdnL causes misregulation of ribosomal and metabolic genes during starvation. Functionally, we demonstrate that the combined action of SR transcriptional regulators and CdnL clearance allows for rapid adaptation to nutrient repletion. We also find that cells that are unable to clear CdnL during starvation are outcompeted by wild-type cells when subjected to fluctuations in nutrients. We hypothesize that post-transcriptional clearance of CdnL during the SR, in conjunction with direct binding of (p)ppGpp and DksA to RNAP, are critical for altering the transcriptome in order to permit cell survival during nutrient stress. Overall design: ChIP-Seq analysis to examine the whole-genome binding/occupancy of CdnL (both the wild type and *DD mutant) in Caulobacter crescentus under normal and depleted carbon conditions.