Ferrichrome outer membrane transporter (FhuA) (FhuA)

Ferrichrome outer membrane transporter (FhuA) is a TonB-dependent receptor primarily found in Gram-negative bacteria such as Escherichia coli. It facilitates the high-affinity uptake of iron-bound ferrichrome, a hydroxamate siderophore, which is essential for bacterial survival in iron-limited environments (UniProt P06971). Structurally, FhuA consists of a 22-stranded beta-barrel occluded by an N-terminal globular plug domain that prevents passive diffusion (PubMed: 9771714). This receptor is a significant therapeutic target because it can be exploited to transport antibiotics into the periplasm, a method known as the Trojan Horse strategy (PubMed: 23143059). Natural examples include albomycin, which mimics ferrichrome to gain entry and inhibit protein synthesis. Additionally, FhuA serves as a docking site for various bacteriophages and colicins, making it a focal point for studying bacterial pathogenesis and developing novel antimicrobial delivery systems (PubMed: 19731224). Targeting FhuA is a promising strategy for overcoming antimicrobial resistance, although mutations in the receptor can lead to decreased drug susceptibility. The specificity of FhuA for certain siderophores makes it a potential candidate for narrow-spectrum antimicrobial development.

Other names

Ferrichrome-iron receptorFerric hydroxamate uptake protein ATonB-dependent siderophore receptorFhuA receptor

Active transport of siderophore-drug conjugates across the outer membrane via the TonB-dependent pathway (Trojan Horse strategy) (PubMed: 19731224).