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Infection and Immunity, November 2005, p. 7252-7258, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7252-7258.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Nickel-Responsive Regulator NikR Controls Activation and Repression of Gene Transcription in Helicobacter pylori

Florian D. Ernst,1 Ernst J. Kuipers,1 Angela Heijens,1 Roya Sarwari,1 Jeroen Stoof,1 Charles W. Penn,2 Johannes G. Kusters,1 and Arnoud H. M. van Vliet1*

Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands,1 School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom2

Received 5 April 2005/ Returned for modification 9 June 2005/ Accepted 4 August 2005

The NikR protein is a nickel-dependent regulatory protein which is a member of the ribbon-helix-helix family of transcriptional regulators. The gastric pathogen Helicobacter pylori expresses a NikR ortholog, which was previously shown to mediate regulation of metal metabolism and urease expression, but the mechanism governing the diverse regulatory effects had not been described until now. In this study it is demonstrated that NikR can regulate H. pylori nickel metabolism by directly controlling transcriptional repression of NixA-mediated nickel uptake and transcriptional induction of urease expression. Mutation of the nickel uptake gene nixA in an H. pylori 26695 nikR mutant restored the ability to grow in Brucella media supplemented with 200 µM NiCl2 but did not restore nickel-dependent induction of urease expression. Nickel-dependent binding of NikR to the promoter of the nixA gene resulted in nickel-repressed transcription, whereas nickel-dependent binding of NikR to the promoter of the ureA gene resulted in nickel-induced transcription. Subsequent analysis of NikR binding to the nixA and ureA promoters showed that the regulatory effect was dependent on the location of the NikR-recognized binding sequence. NikR recognized the region from –13 to +21 of the nixA promoter, encompassing the +1 and –10 region, and this binding resulted in repression of nixA transcription. In contrast, NikR bound to the region from –56 to –91 upstream of the ureA promoter, resulting in induction of urease transcription. In conclusion, the NikR protein is able to function both as a repressor and as an activator of gene transcription, depending on the position of the binding site.

* Corresponding author. Mailing address: Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. Phone: 31-10-463-5944. Fax: 31-10-463-2793. E-mail: a.h.m.vanvliet{at}erasmusmc.nl.

Editor: V. J. DiRita

Infection and Immunity, November 2005, p. 7252-7258, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7252-7258.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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