Abstract
The important human pathogen
Helicobacter pylori
requires the abundant expression and activity of its urease enzyme for colonization of the gastric mucosa. The transcription, expression, and activity of
H. pylori
urease were previously demonstrated to be induced by nickel supplementation of growth media. Here it is demonstrated that the HP1338 protein, an ortholog of the
Escherichia coli
nickel regulatory protein NikR, mediates nickel-responsive induction of urease expression in
H. pylori
. Mutation of the HP1338 gene (
nikR
) of
H. pylori
strain 26695 resulted in significant growth inhibition of the
nikR
mutant in the presence of supplementation with NiCl
2
at ≥100 μM, whereas the wild-type strain tolerated more than 10-fold-higher levels of NiCl
2
. Mutation of
nikR
did not affect urease subunit expression or urease enzyme activity in unsupplemented growth media. However, the nickel-induced increase in urease subunit expression and urease enzyme activity observed in wild-type
H. pylori
was absent in the
H. pylori nikR
mutant. A similar lack of nickel responsiveness was observed upon removal of a 19-bp palindromic sequence in the
ureA
promoter, as demonstrated by using a genomic
ureA
::
lacZ
reporter gene fusion. In conclusion, the
H. pylori
NikR protein and a 19-bp operator sequence in the
ureA
promoter are both essential for nickel-responsive induction of urease expression in
H. pylori
.