Siderophore-mediated iron transport system (SMITS)

The Siderophore-mediated iron transport system is a specialized bacterial machinery used to scavenge ferric iron (Fe3+) from the host environment, where it is typically sequestered by proteins like transferrin and lactoferrin (PMID: 20453874). This system consists of secreted high-affinity chelators called siderophores and their corresponding TonB-dependent receptors (TBDTs) located on the outer membrane of Gram-negative bacteria (UniProt: TonB-dependent receptor family). Upon binding the iron-siderophore complex, the receptor undergoes a conformational change, powered by the TonB-ExbB-ExbD complex, to internalize the iron into the periplasm (PMID: 30111631). This pathway is a critical virulence factor, as iron is essential for bacterial metabolism, DNA synthesis, and biofilm formation. In drug development, this system is exploited through the "Trojan Horse" strategy, where an antibiotic is chemically linked to a siderophore moiety. The most prominent example is Cefiderocol, which utilizes these transporters to bypass the outer membrane, achieving high concentrations at its target site even in multidrug-resistant strains like Pseudomonas aeruginosa (PMID: 31932312).

Other names

Siderophore-iron uptake systemTonB-dependent transport systemBacterial iron acquisition pathwayIron transport via siderophore bindingGO:0033212

Siderophore-mediated active transport (Trojan Horse mechanism) utilizing TonB-dependent receptors to bypass the bacterial outer membrane permeability barrier.