Abstract
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 NiCl
2
resulted in a similar induction of urease activity (at low NiCl
2
concentration) and amidase activity (at ≥500 μM NiCl
2
) 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.