Ferrioxamine B receptor (FoxA) (FoxA)

The Ferrioxamine B receptor (FoxA) is a TonB-dependent outer membrane transporter found in several Gram-negative bacteria, including Pseudomonas aeruginosa and Yersinia enterocolitica, where it facilitates the uptake of the hydroxamate siderophore ferrioxamine B [Moynié et al., 2019, Nature Communications; Jani & Cotter, 2010, Journal of Bacteriology]. Iron is an essential micronutrient for bacterial metabolism and virulence, but its availability is extremely limited in the host environment; thus, FoxA is critical for bacterial survival during infection [Cornelis & Dingemans, 2013, Frontiers in Microbiology]. The transport process involves the high-affinity binding of the iron-siderophore complex to the extracellular loops of FoxA, followed by a TonB-mediated conformational change that allows the complex to pass through the protein's beta-barrel pore [Noinaj et al., 2010, Annual Review of Microbiology]. This transporter is a significant target for the development of siderophore-antibiotic conjugates, often referred to as "Trojan horse" drugs, which utilize the active transport machinery of FoxA to deliver antimicrobial agents directly into the bacterial cell [Mislin & Schalk, 2014, Metallomics]. By exploiting this pathway, these conjugates can overcome the permeability barriers and efflux mechanisms that characterize many multidrug-resistant pathogens [Page, 2019, Antibiotics]. However, therapeutic challenges include the potential for bacteria to develop resistance by downregulating or mutating the FoxA receptor, as well as the presence of alternative iron acquisition pathways that may compensate for its loss [Perkins-Balding et al., 2004, Microbiology and Molecular Biology Reviews].

Other names

FoxAFerrioxamine receptorDesferrioxamine B transporterTonB-dependent ferrioxamine B receptorFerrioxamine B uptake proteinFox system

Siderophore-mediated drug delivery (Trojan horse strategy) involving active transport of antibiotic-siderophore conjugates across the bacterial outer membrane via the TonB-dependent system.