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Infection and Immunity, August 2001, p. 4891-4897, Vol. 69, No. 8
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.8.4891-4897.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Nickel-Responsive Induction of Urease Expression in
Helicobacter pylori Is Mediated at the
Transcriptional Level
Arnoud H. M.
van
Vliet,1,2,*
Ernst J.
Kuipers,2
Barbara
Waidner,3
Beverly J.
Davies,4
Nicolette
de
Vries,1,5,
Charles W.
Penn,4
Christina M. J. E.
Vandenbroucke-Grauls,1
Manfred
Kist,3
Stefan
Bereswill,3 and
Johannes G.
Kusters1,2
Department of Medical Microbiology, Faculty
of Medicine, Vrije Universiteit,1 and
Department of Gastroenterology, Vrije Universiteit Academic
Hospital,5 Amsterdam, and Department of
Gastroenterology and Hepatology, Academic Hospital Dijkzigt,
Rotterdam,2 The Netherlands; Department
of Microbiology, Institute of Medical Microbiology and Hygiene,
University of Freiburg, Freiburg, Germany3; and
School of Biosciences, University of Birmingham, Edgbaston,
Birmingham, United Kingdom4
Received 18 December 2000/Returned for modification 9 February
2001/Accepted 4 May 2001
The nickel-containing enzyme urease is an essential colonization
factor of the gastric pathogen Helicobacter pylori, as it allows the bacterium to survive the acidic conditions in the gastric mucosa. Although urease can represents up to 10% of the total protein
content of H. pylori, expression of urease genes is thought to be constitutive. Here it is demonstrated that H. pylori
regulates the expression and activity of its urease enzyme as a
function of the availability of the cofactor nickel. Supplementation of brucella growth medium with 1 or 100 µM NiCl2 resulted in
up to 3.5-fold-increased expression of the urease subunit proteins UreA and UreB and up to 12-fold-increased urease enzyme activity. The induction was specific for nickel, since the addition of cadmium, cobalt, copper, iron, manganese, or zinc did not affect the expression of urease. Both Northern hybridization studies and a transcriptional ureA::lacZ fusion demonstrated that
the observed nickel-responsive regulation of urease is mediated at the
transcriptional level. Mutation of the HP1027 gene, encoding the ferric
uptake regulator (Fur), did not affect the expression of urease in
unsupplemented medium but reduced the nickel induction of urease
expression to only twofold. This indicates that Fur is involved in the
modulation of urease expression in response to nickel. These data
demonstrate nickel-responsive regulation of H. pylori
urease, a phenomenon likely to be of importance during the colonization
and persistence of H. pylori in the gastric mucosa.
*
Corresponding author. Mailing address: Department of
Gastroenterology and Hepatology, L448, Academic Hospital Dijkzigt,
Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. Phone: 31-10-4635946. Fax: 31-10-4634682. E-mail: vanvliet{at}mdl.azr.nl.

Present address: Department of Gastroenterology and Hepatology,
Academic Hospital Dijkzigt, Rotterdam, The
Netherlands.
Infection and Immunity, August 2001, p. 4891-4897, Vol. 69, No. 8
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.8.4891-4897.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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