Bacterial iron uptake system (None)

The bacterial iron uptake system is a specialized transport machinery used by pathogens to acquire essential ferric iron (Fe3+) from the host environment, where iron is typically sequestered by proteins like transferrin and lactoferrin [2, 4]. This system involves the secretion of high-affinity chelating molecules called siderophores, which bind extracellular iron and are then recognized by specific membrane receptors, such as iron-regulated outer membrane proteins (IROMPs) or TonB-dependent transporters (TBDTs) [1, 6]. In Gram-negative bacteria, the TonB-ExbB-ExbD complex utilizes the proton motive force to energize the transport of these complexes across the outer membrane into the periplasm [2, 3]. This system is a key target for "Trojan Horse" antibiotics, such as cefiderocol, which are conjugated to siderophore-like moieties to facilitate active entry into the bacterial cell, bypassing traditional resistance mechanisms like porin loss or efflux [8, 12]. Cefiderocol specifically exploits transporters like CirA and Fiu in E. coli or PiuA in P. aeruginosa to reach its target, penicillin-binding proteins [5, 8]. While highly effective for drug delivery, the redundancy of iron acquisition pathways and the potential for mutations in transporter genes present significant challenges for long-term therapeutic efficacy [7, 14].

Other names

Iron-uptake systemSiderophore-mediated iron transport systemTonB-dependent transport systemFerric iron transporter systemIron acquisition system

Active transport of siderophore-drug conjugates into the bacterial cell via iron-regulated transporters (Trojan Horse strategy).