Gram-negative bacterial iron transport protein (TBDR)

Gram-negative bacterial iron transport proteins, primarily TonB-dependent receptors (TBDRs), are essential outer membrane transporters that facilitate the uptake of iron-siderophore complexes (Noinaj et al., 2010, Nature Reviews Microbiology). Since iron is a critical micronutrient for bacterial survival and virulence, these proteins are vital for establishing infections in the host (Cornelis, 2010, Natural Product Reports). These transporters are exploited by Trojan horse antibiotics, such as cefiderocol, which mimic siderophores to gain entry into the bacterial periplasm, bypassing traditional resistance mechanisms like porin loss (Zhanel et al., 2019, Drugs). The TonB-ExbB-ExbD complex provides the necessary energy for this active transport process across the outer membrane (Postle & Kadner, 2003, Annual Review of Microbiology). Targeting these systems is a key strategy for addressing multi-drug resistant (MDR) pathogens like Acinetobacter baumannii and Pseudomonas aeruginosa (Page, 2019, Annals of the New York Academy of Sciences). These proteins are highly regulated by the Ferric Uptake Regulator (Fur) protein, which ensures their expression is upregulated under iron-limited conditions typical of the human host (Fillat, 2014, BioMetals). Therapeutic interventions targeting these proteins include both direct inhibition of transport and the use of siderophore-drug conjugates to deliver bactericidal payloads (Krewulak & Vogel, 2008, Biochimica et Biophysica Acta).

Other names

TonB-dependent receptorSiderophore receptorOuter membrane iron transporterIron-regulated outer membrane proteinIROMPFerric siderophore receptor

Siderophore-mediated active transport (Trojan horse mechanism) where the drug mimics a siderophore to gain entry into the bacterial cell via iron transporters (Zhanel et al., 2019, Drugs).