Abstract
Ferric uptake regulator (Fur) is a transcriptional regulator playing a central role in iron homeostasis of many bacteria, and Fur inactivation commonly results in pleiotropic phenotypes. In Shewanella oneidensis, a representative of dissimilatory metal-reducing γ-proteobacteria capable of respiring a variety of chemicals as electron acceptors (EAs), Fur loss substantially impairs respiration. However, to date the mechanism underlying the physiological phenomenon remains obscure. This investigation reveals that Fur loss compromises activity of iron proteins requiring biosynthetic processes for their iron cofactors, heme in particular. We then show that S. oneidensis Fur is critical for maintaining heme homeostasis by affecting both its biosynthesis and decomposition of the molecule. Intriguingly, the abundance of iron-containing proteins controlled by H2O2-responding regulator OxyR increases in the fur mutant because the Fur loss activates OxyR. By comparing suppression of membrane-impermeable, membrane-permeable, and intracellular-only iron chelators on heme deficiency and elevated H2O2 resistance, our data suggest that the elevation of the free iron content by the Fur loss is likely to be the predominant factor for the Fur physiology. Overall, these results provide circumstantial evidence that Fur inactivation disturbs bacterial iron homeostasis by altering transcription of its regulon members, through which many physiological processes, such as respiration and oxidative stress response, are transformed.
Highlights
Iron is a critical nutrient for virtually all living organisms to survive and grow as it is the most common redox active metal found in proteins (Andrews et al, 2003)
Ferric uptake regulator (Fur) proteins are regarded as global transcriptional regulators, controlling a large number of genes participating in diverse biological processes, such as redox regulation, energy metabolism, defenses against oxidative and nitrosative stresses, nucleic acid biosynthesis, cell morphology and motility, and many more (Jittawuttipoka et al, 2010; Yu and Genco, 2012; Becerra et al, 2014; Fillat, 2014; González et al, 2014; Seo et al, 2014; Pasqua et al, 2017)
Fur inactivation imposes upon bacterial cells an inability to maintain normal iron homeostasis, resulting in altered iron contents that triggers an array of physiological abnormalities
Summary
Iron is a critical nutrient for virtually all living organisms to survive and grow as it is the most common redox active metal found in proteins (Andrews et al, 2003). Because of high demand and low solubility of iron in aerobic environments, iron acquisition has always been a challenge to cells, causing iron deficiency to be one of the most common nutritional stresses (Frawley and Fang, 2014). When overloaded, iron could be highly toxic to cells by efficiently catalyzing biomolecular damages to DNA, proteins, and lipids. Fur Biology in S. oneidensis via Fenton reaction (Imlay, 2013). Given that both iron deficiency and overload can be deleterious, it is imperative that cells maintain proper iron homeostasis (Andrews et al, 2003)
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