Regulation of ferritin-mediated cytoplasmic iron storage by the ferric uptake regulator homolog (Fur) of Helicobacter pylori

Homologs of the ferric uptake regulator Fur and the iron storage protein fe rritin play a central role in maintaining iron homeostasis in bacteria. The gastric pathogen Helicobacter pylori contains an iron-induced prokaryotic ferritin (Pfr) which has been shown to be involved in protection against me tal toxicity and a Fur homolog which has not been functionally characterize d in H. pylori. Analysis of an isogenic fur-negative mutant revealed that H . pylori Fur is required for metal-dependent regulation of ferritin. Iron s tarvation, as well as medium supplementation with nickel, zinc, copper, and manganese at nontoxic concentrations, repressed synthesis of ferritin in t he wild-type strain but not in the H. pylori fur mutant. Fur-mediated regul ation of ferritin synthesis occurs at the mRNA level. With respect to the r egulation of ferritin expression, Fur behaves like a global metal-dependent repressor which is activated under iron-restricted conditions but also res ponds to different metals. Downregulation of ferritin expression by Fur mig ht secure the availability of free iron in the cytoplasm, especially if iro n is scarce or titrated out by other metals.