Bacterial iron-siderophore transporter (TBDT)

Bacterial iron-siderophore transporters are specialized outer membrane proteins, primarily TonB-dependent transporters (TBDTs), that facilitate the uptake of iron-siderophore complexes into Gram-negative bacteria [1]. Since iron is essential for bacterial growth and pathogenesis but is sequestered by host proteins like transferrin, bacteria secrete high-affinity chelators called siderophores to scavenge ferric iron [2]. These transporters then recognize and actively transport the iron-siderophore complexes across the outer membrane, a process powered by the TonB-ExbB-ExbD protein complex [3]. Because these transporters are upregulated under iron-limited conditions typical of an infection, they serve as effective entry points for antimicrobial agents [4]. The Trojan horse strategy utilizes these transporters by conjugating antibiotics to siderophore-like moieties, as seen with the FDA-approved drug cefiderocol [5]. This approach allows the drug to bypass traditional porin channels, overcoming common resistance mechanisms and delivering the antibiotic directly into the periplasmic space [6].

Other names

TonB-dependent transporterSiderophore receptorFerric-siderophore transporterOuter membrane iron transporterTonB-dependent receptor

Siderophore-mediated active transport (Trojan horse mechanism)