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Journal of Bacteriology, November 2008, p. 7326-7334, Vol. 190, No. 22
0021-9193/08/$08.00+0 doi:10.1128/JB.00903-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
,
Hyunkeun Kim,1,
Jiae Yun,2
Sangryeol Ryu,2
Eduardo A. Groisman,3 and
Dongwoo Shin1*
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea,1 Department of Food and Animal Biotechnology, Department of Agricultural Biotechnology, and Center for Agricultural Biomaterials, Seoul National University, Seoul 151-921, South Korea,2 Department of Molecular Microbiology, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 631103
Received 30 June 2008/ Accepted 31 August 2008
The Fur protein is a primary regulator that monitors and controls cytoplasmic iron levels. We now report the identification of a regulatory pathway mediated by the Salmonella response regulator RstA that promotes Fur activity. Genome-wide expression experiments revealed that under iron-replete conditions, expression of the RstA protein from a plasmid lowered transcription levels of various genes involved in iron acquisition. The RstA protein controlled iron-responsive genes through the Fur-Fe(II) protein because deletion of the fur gene or iron depletion abrogated RstA-mediated repression of these genes. The RstA protein maintained wild-type levels of the Fur protein but exceptionally activated transcription of the feoAB operon encoding the ferrous iron transporter FeoB by binding directly to the feoA promoter. This FeoB induction resulted in increased ferrous iron uptake, which associates with the Fur protein because lack of RstA-dependent transcriptional activation of the feoA promoter and feoB-deletion abolished repression of the Fur target genes by the RstA protein. Under iron-replete conditions, RstA expression retarded Salmonella growth but enabled the Fur protein to repress the target genes beyond the levels which were simply accomplished by iron.
Published ahead of print on 12 September 2008.
Supplemental material for this article may be found at http://jb.asm.org/.
J.J. and H.K. contributed equally to this work.
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