title: Essential role of ferritin Pfr in Helicobacter pylori iron metabolism and gastric colonization.
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.
authors.affiliation: Institute of Medical Microbiology and Hygiene, Department of Medical Microbiology and Hygiene, University Hospital of Freiburg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Waidner
authors.forename: Stefan
authors.initials: S
authors.lastname: Greiner
authors.forename: Stefan
authors.initials: S
authors.lastname: Odenbreit
authors.forename: Holger
authors.initials: H
authors.lastname: Kavermann
authors.forename: Jyoti
authors.initials: J
authors.lastname: Velayudhan
authors.forename: Frank
authors.initials: F
authors.lastname: Stähler
authors.forename: Johannes
authors.initials: J
authors.lastname: Guhl
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bissé
authors.forename: Arnoud H M
authors.initials: AH
authors.lastname: van Vliet
authors.forename: Simon C
authors.initials: SC
authors.lastname: Andrews
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Kusters
authors.forename: David J
authors.initials: DJ
authors.lastname: Kelly
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
authors.forename: Manfred
authors.initials: M
authors.lastname: Kist
authors.forename: Stefan
authors.initials: S
authors.lastname: Bereswill
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001692:Biological Transport; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005293:Ferritins / Q000031:analogs & derivatives* / Q000235:genetics / Q000502:physiology*; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000378:metabolism*; D016296:Mutagenesis; D018384:Oxidative Stress; D010269:Paraquat / Q000494:pharmacology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013270:Stomach / Q000382:microbiology*; D013481:Superoxides / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D027682:Cation Transport Proteins; C414315:FeoB protein, Helicobacter pylori; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; C431650:pfr protein, Helicobacter pylori; D013481:Superoxides; D005293:Ferritins; D007501:Iron; D010269:Paraquat