Abstract
The reactivity of the essential element iron necessitates a concerted expression of ferritins, which mediate iron storage in a nonreactive state. Here we have further established the role of the
Helicobacter pylori
ferritin Pfr in iron metabolism and gastric colonization. Iron stored in Pfr enabled
H. pylori
to multiply under severe iron starvation and protected the bacteria from acid-amplified iron toxicity, as inactivation of the
pfr
gene restricted growth of
H. pylori
under these conditions. The lowered total iron content in the
pfr
mutant, which is probably caused by decreased iron uptake rates, was also reflected by an increased resistance to superoxide stress. Iron induction of Pfr synthesis was clearly diminished in an
H. pylori feoB
mutant, which lacked high-affinity ferrous iron transport, confirming that Pfr expression is mediated by changes in the cytoplasmic iron pool and not by extracellular iron. This is well in agreement with the recent discovery that iron induces Pfr synthesis by abolishing Fur-mediated repression of
pfr
transcription, which was further confirmed here by the observation that iron inhibited the in vitro binding of recombinant
H. pylori
Fur to the
pfr
promoter region. The functions of
H. pylori
Pfr in iron metabolism are essential for survival in the gastric mucosa, as the
pfr
mutant was unable to colonize in a Mongolian gerbil-based animal model. In summary, the
pfr
phenotypes observed give new insights into prokaryotic ferritin functions and indicate that iron storage and homeostasis are of extraordinary importance for
H. pylori
to survive in its hostile natural environment.