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Infection and Immunity, February 2007, p. 745-752, Vol. 75, No. 2
0019-9567/07/$08.00+0     doi:10.1128/IAI.01163-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Iron-Responsive Repression of Urease Expression in Helicobacter hepaticus Is Mediated by the Transcriptional Regulator Fur{triangledown}

Clara Belzer, Bart A. M. van Schendel, Ernst J. Kuipers, Johannes G. Kusters, and Arnoud H. M. van Vliet*

Department of Gastroenterology and Hepatology, Erasmus MC—University Medical Center, Rotterdam, The Netherlands

Received 25 July 2006/ Returned for modification 8 September 2006/ Accepted 2 November 2006

Persistent colonization of mucosal surfaces by bacteria in the mammalian host requires concerted expression of colonization factors, depending on the environmental conditions. Helicobacter hepaticus is a urease-positive pathogen that colonizes the intestinal and hepatobiliary tracts of rodents. Here it is reported that urease expression of H. hepaticus is iron repressed by the transcriptional regulator Fur. Iron restriction of growth medium resulted in a doubling of urease activity in wild-type H. hepaticus strain ATCC 51449 and was accompanied by increased levels of urease subunit proteins and ureA mRNA. Insertional inactivation of the fur gene abolished iron-responsive repression of urease activity, whereas inactivation of the perR gene did not affect iron-responsive regulation of urease activity. The iron-responsive promoter element was identified directly upstream of the H. hepaticus ureA gene. Recombinant H. hepaticus Fur protein bound to this ureA promoter region in a metal-dependent matter, and binding resulted in the protection of a 41-bp, Fur box-containing operator sequence located at positions –35 to –75 upstream of the transcription start site. In conclusion, H. hepaticus Fur controls urease expression at the transcriptional level in response to iron availability. This represents a novel type of urease regulation in ureolytic bacteria and extends the already diverse regulatory repertoire of the Fur protein.


* Corresponding author. Mailing address: Department of Gastroenterology and Hepatology, Erasmus MC—University Medical Center, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. Phone: 31-10-463-5944. Fax: 31-10-463-2793. E-mail: a.h.m.vanvliet{at}erasmusmc.nl.

{triangledown} Published ahead of print on 13 November 2006.

Editor: V. J. DiRita


Infection and Immunity, February 2007, p. 745-752, Vol. 75, No. 2
0019-9567/07/$08.00+0     doi:10.1128/IAI.01163-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.