Ferrioxamine B receptor (FoxA)

Bacterial iron-siderophore complex transporters recognizing desferrioxamine-B are specialized protein systems used by various bacteria to scavenge iron, an essential nutrient for survival and pathogenesis (PMID: 25344618). These transporters, such as FoxA in Pseudomonas aeruginosa and FhuE in Escherichia coli, are TonB-dependent outer membrane receptors that specifically bind ferrioxamine-B, the iron-bound form of the siderophore desferrioxamine-B (UniProt: P42513, P06975). Upon binding, the receptor undergoes a conformational change powered by the TonB-ExbB-ExbD complex to transport the iron-siderophore complex into the periplasmic space (PMID: 30254217). From the periplasm, the complex is further transported into the cytoplasm by specific ATP-binding cassette (ABC) transporters. These systems are highly regulated by environmental iron availability, typically being upregulated under iron-starved conditions common during host infection. In drug development, these transporters are exploited via the Trojan Horse strategy, where antibiotics are chemically linked to desferrioxamine-B to ensure active uptake into the bacterial cell (PMID: 28845631). This mechanism allows drugs to bypass the restrictive outer membrane of Gram-negative bacteria, potentially overcoming resistance due to low permeability or efflux. Research into these transporters is vital for developing new treatments against multi-drug resistant pathogens like Pseudomonas aeruginosa and Acinetobacter baumannii.

Other names

FoxAFhuEDesferrioxamine B transporterFerrioxamine uptake proteinTonB-dependent ferrioxamine receptorSiderophore transport protein FoxA

Siderophore-mediated drug delivery (Trojan Horse strategy) utilizing active transport to bypass the bacterial outer membrane barrier.