The UzcRS two-component system in Caulobacter crescentus integrates regulatory input from diverse auxiliary regulators

Mol Microbiol. 2019 Mar;111(3):678-699. doi: 10.1111/mmi.14180. Epub 2019 Feb 3.


The UzcRS two-component system in Caulobacter crescentus mediates widespread transcriptional activation in response to the metals U, Zn and Cu. Unexpectedly, a screen for mutations that affected the activity of the UzcR-regulated urcA promoter (PurcA ) revealed four previously uncharacterized proteins whose inactivation led to metal-independent induction of PurcA . Using molecular genetics and functional genomics, we find that these auxiliary regulators control PurcA expression by modulating the activity of UzcRS through distinct mechanisms. An ABC transporter with a periplasmic metallo-aminopeptidase domain forms a sensory complex with UzcRS, antagonizing metal dependent stimulation by virtue of its ATPase and peptidase domains. Two MarR-like transcription factors synergistically regulate UzcRS activity by repressing the expression of the membrane proteins UzcY and UzcZ, which stimulate UzcRS activity and enhance its sensitivity to a more environmentally relevant U/Zn/Cu concentration range. Additionally, the membrane protein UzcX, whose expression is positively regulated by UzcR, provides a mechanism of feedback inhibition within the UzcRS circuit. Collectively, these data suggest that UzcRS functions as the core-signaling unit within a multicomponent signal transduction pathway that includes a diverse set of auxiliary regulators, providing further insight into the complexity of signaling networks.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacterial Proteins / metabolism*
  • Biological Transport, Active
  • Caulobacter crescentus / drug effects*
  • Caulobacter crescentus / genetics*
  • Gene Expression Regulation, Bacterial*
  • Membrane Transport Proteins / metabolism
  • Metals, Heavy / metabolism*
  • Signal Transduction*
  • Transcription Factors / metabolism*
  • Transcription, Genetic


  • Bacterial Proteins
  • Membrane Transport Proteins
  • Metals, Heavy
  • Transcription Factors