Roles of the EnvZ/OmpR Two-Component System and Porins in Iron Acquisition in .

secretes high-affinity Fe chelators to solubilize and transport chelated Fe via specific outer membrane receptors. In microaerobic and anaerobic growth environments, where the reduced Fe form is predominant, ferrous transport systems fulfill the bacterial need for iron. Expression of genes coding for iron metabolism is controlled by Fur, which when bound to Fe acts as a repressor. Work carried out here shows that the constitutively activated EnvZ/OmpR two-component system, which normally controls expression of the and porin genes, dramatically increases the intracellular pool of accessible iron, as determined by whole-cell electron paramagnetic resonance spectroscopy, by inducing the OmpC/FeoB-mediated ferrous transport pathway. Elevated levels of intracellular iron in turn activated Fur, which inhibited the ferric transport pathway but not the ferrous transport pathway. The data show that the positive effect of constitutively activated EnvZ/OmpR on expression is sufficient to overcome the negative effect of activated Fur on In a mutant, which lacks functional ferric transport systems, deletion of severely impairs growth on rich medium not supplemented with iron, while the simultaneous deletion of and is not viable. These data, together with the observation of derepression of the Fur regulon in an OmpC mutant, show that the porins play an important role in iron homeostasis. The work presented here also resolves a long-standing paradoxical observation of the effect of certain mutant alleles on iron regulon. The work presented here solved a long-standing paradox of the negative effects of certain missense alleles of , which codes for kinase of the EnvZ/OmpR two-component system, on the expression of ferric uptake genes. The data revealed that the constitutive alleles activate the Feo- and OmpC-mediated ferrous uptake pathway to flood the cytoplasm with accessible ferrous iron. This activates the ferric uptake regulator, Fur, which inhibits ferric uptake system but cannot inhibit the operon due to the positive effect of activated EnvZ/OmpR. The data also revealed the importance of porins in iron homeostasis.