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Infection and Immunity, February 2004, p. 766-773, Vol. 72, No. 2
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.2.766-773.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Acid-Responsive Gene Induction of Ammonia-Producing Enzymes in Helicobacter pylori Is Mediated via a Metal-Responsive Repressor Cascade

Arnoud H. M. van Vliet,* Ernst J. Kuipers, Jeroen Stoof, Sophie W. Poppelaars, and Johannes G. Kusters

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

Received 29 September 2003/ Accepted 15 October 2003

Although the adaptive mechanisms allowing the gastric pathogen Helicobacter pylori to survive acid shocks have been well documented, the mechanisms allowing growth at mildly acidic conditions (pH ~5.5) are still poorly understood. Here we demonstrate that H. pylori strain 26695 increases the transcription and activity of its urease, amidase, and formamidase enzymes four- to ninefold in response to growth at pH 5.5. Supplementation of growth medium with NiCl2 resulted in a similar induction of urease activity (at low NiCl2 concentration) and amidase activity (at >=500 µM NiCl2) but did not affect formamidase activity. Mutation of the fur gene, which encodes an iron-responsive repressor of both amidases, resulted in a constitutively high level of amidase and formamidase activity at either pH but did not affect urease activity at pH 7.0 or pH 5.5. In contrast, mutation of the nikR gene, encoding the nickel-responsive activator of urease expression, resulted in a significant reduction of acid-responsive induction of amidase and formamidase activity. Finally, acid-responsive repression of fur transcription was absent in the H. pylori nikR mutant, whereas transcription of the nikR gene itself was increased at pH 5.5 in wild-type H. pylori. We hypothesize that H. pylori uses a repressor cascade to respond to low pH, with NikR initiating the response directly via the urease operon and indirectly via the members of the Fur regulon.


* Corresponding author. Mailing address: Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Room L-459, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. Phone: 31-10-4635944. Fax: 31-10-4632793. E-mail: a.h.m.vanvliet{at}erasmusmc.nl.

Editor: V. J. DiRita


Infection and Immunity, February 2004, p. 766-773, Vol. 72, No. 2
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.2.766-773.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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