Identification of a U/Zn/Cu responsive global regulatory two‐component system in Caulobacter crescentus. Issue 1 (23rd January 2017)

• Record Type: Journal Article
• Authors: Park, Dan M.; Overton, K. Wesley; Liou, Megan J.; Jiao, Yongqin
• Is Part Of: Molecular microbiology. Volume 104:Issue 1(2017)
• Page Start: 46
• Page End: 64
• Publication Date: 2017-01-23
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.13615
• Languages: English
• ISSNs: 0950-382X

Abstract

Summary: 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 (P urcA ) 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 P urcA . 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. Abstract : This study was initiated to examine uranium (U) sensing and response in Caulobacter crescentus, a bacterium that is U tolerant. We identified a previously uncharacterized two‐component system, UzcRS, which is highly responsive to zinc, copper and uranium. Using genome‐scale analyses, we found that UzcR is a global activator of genes associated with a novel extracytoplasmic stress response pathway.