title: Identification of a U/Zn/Cu responsive global regulatory two-component system in Caulobacter crescentus.
abstract: Despite the well-known toxicity of uranium (U) to bacteria, little is known about how cells sense and respond to U. The recent finding of a U-specific stress response in Caulobacter crescentus has provided a foundation for studying the mechanisms of U- perception in bacteria. To gain insight into this process, we used a forward genetic screen to identify the regulatory components governing expression of the urcA promoter (PurcA) that is strongly induced by U. This approach unearthed a previously uncharacterized two-component system, named UzcRS, which is responsible for U-dependent activation of PurcA. UzcRS is also highly responsive to zinc and copper, revealing a broader specificity than previously thought. Using ChIP-seq, we found that UzcR binds extensively throughout the genome in a metal-dependent manner and recognizes a noncanonical DNA-binding site. Coupling the genome-wide occupancy data with RNA-seq analysis revealed that UzcR is a global regulator of transcription, predominately activating genes encoding proteins that are localized to the cell envelope; these include metallopeptidases, multidrug-resistant efflux (MDR) pumps, TonB-dependent receptors and many proteins of unknown function. Collectively, our data suggest that UzcRS couples the perception of U, Zn and Cu with a novel extracytoplasmic stress response.
authors.affiliation: Biosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA, USA.
authors.forename: Dan M
authors.initials: DM
authors.lastname: Park
authors.affiliation: Biosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA, USA.
authors.forename: K Wesley
authors.initials: KW
authors.lastname: Overton
authors.affiliation: Biosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA, USA.
authors.forename: Megan J
authors.initials: MJ
authors.lastname: Liou
authors.affiliation: Biosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA, USA.
authors.forename: Yongqin
authors.identifier: 0000-0002-6798-5823
authors.initials: Y
authors.lastname: Jiao
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D016935:Caulobacter crescentus / Q000235:genetics* / Q000378:metabolism*; D003300:Copper / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D011401:Promoter Regions, Genetic / Q000235:genetics; D050436:Regulatory Elements, Transcriptional / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D013312:Stress, Physiological; D014158:Transcription, Genetic / Q000235:genetics; D014501:Uranium / Q000378:metabolism; D015032:Zinc / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D014501:Uranium; D003300:Copper; D015032:Zinc