Molecular Adaptations of Ferric Uptake Regulator (Fur) Proteins Drive Iron Homeostasis and Pathogenesis in Vibrio Spp

Ferric uptake regulator (Fur) mediates iron homeostasis in bacteria, but its applicability extends far beyond the canonical iron-responsive repression in Vibrio. Substantial structural, functional, and regulatory divergence exists across Vibrio species inhabiting marine and host-associated niches. This review synthesizes our current understanding of the Vibrio Fur regulon, emphasizing non-canonical mechanisms, including Fur-mediated transcriptional activation, interactions with accessory regulators, integration with small regulatory RNAs, and coordination with global metabolic and stress response pathways. We examine how Fur integrates multiple environmental cues, such as iron availability, temperature fluctuations, carbon metabolism, and quorum sensing to control iron acquisition, biofilm formation, virulence factor production, and environmental persistence. Phylogenetic analysis revealed species-specific adaptations of Fur underlying ecological fitness and pathogenicity in marine, zoonotic, and human pathogenic Vibrio spp. We discuss implications for host-pathogen interactions and Fur’s potential as an antivirulence target against antibiotic-resistant Vibrio infections. Together, these findings position Fur as a master regulator linking metabolism, environmental adaptation, and virulence in Vibrio.