Which bacterial regulatory system is activated under iron-limited conditions?
Iron is essential micronutrient serving as cofactor for cytochromes of electron transport chain, iron-sulfur proteins like ferredoxin and aconitase, heme enzymes and many dehydratases yet its free concentration is extremely limited in host due to sequestration by transferrin, lactoferrin and ferritin and is toxic at high levels via Fenton reaction generating hydroxyl radicals. Under iron-limited conditions commonly encountered in serum and mucosal surfaces, bacteria derepress high-affinity iron acquisition machineries controlled by Ferric uptake regulator Fur, a global metalloregulatory protein. Fur is a homodimeric iron-dependent repressor that when bound to Fe2+ as corepressor dimer binds with high affinity to 19-base pair Fur box consensus GATAATGATAATCATTATC sequence upstream of iron-regulated genes, physically blocking RNA polymerase binding for genes encoding siderophore biosynthesis pathways such as enterobactin via ent operon, TonB-dependent outer membrane receptors FepA and FhuA, heme uptake systems Chu and Feo ferrous transport. When iron concentrations drop, Fur loses Fe2+, undergoes allosteric change, dissociates from DNA, allowing transcription of siderophore systems and small regulatory RNAs RyhB that downregulate iron-consuming pathways like TCA cycle and iron storage. OxyR senses peroxide, PhoP-PhoQ senses magnesium limitation, SoxR senses superoxide, distinct from Fur-mediated iron homeostasis critical for virulence and colonization.
Ref: Madigan et al., Brock Biology of Microorganisms, 16th ed., Chapter 7: Fur System and Iron Limitation Response.