Ferric uptake regulator (Fur)

The Ferric uptake regulator (Fur) is a global transcriptional repressor found in a wide variety of bacteria, where it plays a central role in maintaining iron homeostasis (UniProt P0A9A9). It functions as a homodimer that, in the presence of sufficient intracellular ferrous iron (Fe2+), binds to specific DNA sequences known as Fur boxes to repress the transcription of genes involved in iron acquisition, such as siderophores and iron transporters (PubMed: 11544354). Beyond iron metabolism, Fur is known to regulate genes associated with the oxidative stress response, acid tolerance, and the expression of various virulence factors, making it essential for bacterial survival and pathogenesis within the host environment (PubMed: 19129923). Because Fur is critical for the virulence of many human pathogens and lacks a direct human homolog, it is considered a high-priority target for the development of novel antimicrobial agents (PubMed: 26161574). Therapeutic strategies targeting Fur include small molecule inhibitors that prevent DNA binding or metal-mimetic compounds like Gallium that disrupt iron-dependent regulatory cycles (PubMed: 23533140). Inhibiting Fur can lead to iron toxicity or iron starvation and significantly reduce the pathogenicity of bacteria like Pseudomonas aeruginosa and Helicobacter pylori. This makes it a promising candidate for addressing antibiotic resistance in Gram-negative pathogens.

Other names

Ferric uptake regulation proteinIron-dependent transcriptional repressor FurFUR

Inhibition of Fur-DNA binding or disruption of the iron-sensing mechanism to deregulate bacterial iron metabolism and attenuate virulence (PubMed: 26161574).