Ferric uptake regulator (Fur) (Fur)

The Ferric uptake regulator (Fur) is a 150-amino acid metalloregulatory protein that serves as a master transcriptional regulator in Helicobacter pylori. It primarily functions by sensing intracellular iron levels using ferrous iron (Fe2+) as a cofactor to bind specific DNA sequences known as Fur boxes, thereby repressing or activating genes involved in iron acquisition, storage, and metabolism. Beyond iron homeostasis, Fur is critical for H. pylori's adaptation to the harsh gastric environment, regulating genes essential for acid resistance, oxidative stress defense, and salt stress response. Because Fur is essential for successful colonization and persistence within the human stomach, it is a significant factor in the pathogenesis of gastritis, peptic ulcers, and gastric adenocarcinoma. Bismuth-based drugs, such as colloidal bismuth subcitrate, exert their antimicrobial effects in part by targeting Fur; bismuth ions (Bi3+) displace zinc from the protein's structural site, inducing oligomerization and abolishing its DNA-binding capability. This disruption of the Fur-mediated regulatory network severely impairs bacterial physiology, making it an attractive target for overcoming antibiotic resistance in H. pylori infections.

Other names

HP0102Ferric uptake regulation proteinHpFurFerric uptake regulator protein

Bismuth ions (Bi3+) bind to the Fur protein at the S1 metal-binding site, displacing zinc ions and inducing protein oligomerization. This structural change abolishes the protein's DNA-binding capability, leading to the derepression of iron-uptake genes and the disruption of global regulatory networks essential for bacterial survival and colonization.