NikR Mediates Nickel-Responsive Transcriptional Induction of Urease Expression inHelicobacter pylori

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Abstract
The important human pathogenHelicobacter pylorirequires the abundant expression and activity of its urease enzyme for colonization of the gastric mucosa. The transcription, expression, and activity ofH. pyloriurease were previously demonstrated to be induced by nickel supplementation of growth media. Here it is demonstrated that the HP1338 protein, an ortholog of theEscherichia colinickel regulatory protein NikR, mediates nickel-responsive induction of urease expression inH. pylori. Mutation of the HP1338 gene (nikR) ofH. pyloristrain 26695 resulted in significant growth inhibition of thenikRmutant in the presence of supplementation with NiCl2at ≥100 μM, whereas the wild-type strain tolerated more than 10-fold-higher levels of NiCl2. Mutation ofnikRdid 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-typeH. pyloriwas absent in theH. pylori nikRmutant. A similar lack of nickel responsiveness was observed upon removal of a 19-bp palindromic sequence in theureApromoter, as demonstrated by using a genomicureA::lacZreporter gene fusion. In conclusion, theH. pyloriNikR protein and a 19-bp operator sequence in theureApromoter are both essential for nickel-responsive induction of urease expression inH. pylori.