Siderophore receptor and porin proteins (TBDR/OMP)

Siderophore receptor and porin proteins are essential outer membrane components of Gram-negative bacteria that serve as the primary gateways for nutrient acquisition and molecular entry. Siderophore receptors, primarily TonB-dependent receptors (TBDRs), facilitate the active transport of iron-siderophore complexes across the outer membrane, a process powered by the TonB-ExbB-ExbD complex in the inner membrane (PMID: 22403408). Porins are protein channels that allow the passive diffusion of small, hydrophilic molecules, including many classes of antibiotics like beta-lactams and fluoroquinolones (PMID: 12654431). These proteins are exploited by "Trojan Horse" antibiotics, such as Cefiderocol, which mimics a siderophore to be actively transported into the periplasm, thereby bypassing common resistance mechanisms like porin loss or efflux pump upregulation (PMID: 30718271). Targeting these proteins is a critical strategy for treating multi-drug resistant (MDR) infections caused by pathogens like Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae (PMID: 31533998). Resistance to drugs targeting these proteins often arises through the downregulation of porins or mutations in the siderophore transport machinery, presenting a significant therapeutic challenge.

Other names

TonB-dependent receptorsOuter membrane porinsIron-siderophore transportersBacterial outer membrane proteins

Siderophore-mediated active transport (Trojan Horse mechanism) and passive diffusion through porin channels