Independent and cooperative regulation of staphylopine biosynthesis and trafficking by Fur and Zur. Issue 2 (26th February 2018)

• Record Type: Journal Article
• Authors: Fojcik, Clémentine; Arnoux, Pascal; Ouerdane, Laurent; Aigle, Marina; Alfonsi, Laura; Borezée‐Durant, Elise
• Is Part Of: Molecular microbiology. Volume 108:Issue 2(2018)
• Page Start: 159
• Page End: 177
• Publication Date: 2018-02-26
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.13927
• Languages: English
• ISSNs: 0950-382X

Abstract

Summary: Staphylococcus aureus expresses the Cnt system implicated in the active transport of trace metals by synthesizing (CntKLM) and exporting (CntE) staphylopine, a metallophore chelating metals and then taken up by an ABC‐transporter (CntABCDF). This machinery is encoded in the cntKLMABCDFE operon, preceded by a non‐coding region (P cntK ) and containing an internal promoter region (P cntA ). P cntK comprises a Fur box followed by a Zur box, a sRNA transcription start and a repeated region, while P cntA comprises a Fur box that overlaps a Zur box. We found that P cntK promoter activity is attenuated by the repeated sequence and strictly controlled by Fur or Zur binding to its respective target sequences. Interestingly, we discovered a cooperative regulation of the P cntA activity by both Fur and Zur binding to the Fur/Zur box, by identifying a tripartite complex with DNA. Repression of P cntA is less sensitive to metal concentration and therefore loosely repressed as compared to P cntK activity. Furthermore, the Cnt system is essential for the optimal import of zinc, thereby linking regulation and function of Cnt. Overall, our results highlight the need for fine and differential tuning of staphylopine biosynthesis and trafficking in order to efficiently respond to metal starvation and optimize metal recovery. Abstract : The staphylopine‐dependent metal uptake system Cnt of Staphylococcus aureus is encoded by nine genes organized in an operon containing two promoter regions. We describe a double‐level regulation by Fur and Zur regulators, with strict control of staphylopine synthesis by low levels of iron and zinc and looser repression of Cnt transporters by the same metals. This latter control is exerted by both regulators on the same target sequence in an original way. Zinc and iron are the regulatory and substrate metals of Cnt, linking expression and function of the Cnt system.